Rapid Anterograde Spread of Premitotic Activity Along Degenerating Cat Sciatic Nerve

Peripheral nerve transection triggers a series of phenotypic alterations in Schwann cells distal to the site of injury. Mitosis is one of the earliest and best characterized of these responses, although the mechanism by which axonal damage triggers this critical event is unknown. This study examines the appearance and spatio-temporal spread of premitotic activity in distal stumps of transected cat tibial nerves. Premitotic activity was determined by measuring incorporation of [3H]thymidine (a marker of DNA synthesis during the S-phase of the cell cycle) into consecutive segments of desheathed tibial nerve. Incorporation of [3H]thymidine spread proximo-distally within distal nerve stumps between 3 and 4 days posttransection with an apparent velocity of at least 199 +/- 67 mm/day. This suggests that anterograde fast axonal transport may directly or indirectly be associated with the Schwann cell mitotic response to axon transection.     

Effect of Wallerian Degeneration on Histamine Concentration of the Peripheral Nerve

One sciatic nerve of a White Leghorn hen was severed and the distal portion was allowed to undergo Wallerian degeneration. The change in histamine and DNA concentration and mast cell number was measured at different times following nerve sectioning in the proximal regenerating, distal degenerating, and intact, contralateral nerves. The experimental results revealed a significant accumulation of histamine in the proximal desheathed segment and in the contralateral “functional nerve,” whereas the biogenic amine in the distal desheathed nerve significantly decreased. The pattern of change of histamine in the distal and proximal nerve sheaths was different: it dropped at 2 h and then rose in the later stages of Wallerian degeneration. In the distal desheathed nerves and in both the proximal and distal nerve sheaths DNA increased significantly by 14 days. The number of mast cells appeared to be highest in the 14-day distal nerve and in the 7-day proximal nerve sheaths. These results support a dual localization of histamine in the peripheral nerve, and are consistent with the interpretation that the amine has either some role in neurotransmission or in the process of growth and regeneration.     

Early and Dose-Dependent Decrease of Retrograde Axonal Transport in Acrylamide-Intoxicated Rats

The effect of retrograde axonal transport of doses of acrylamide ranging from 50 to 500 mg/kg was studied in sensory nerve of rats. Accumulation of trichloroacetic acid-phosphotungstic acid-insoluble label was measured in a collection segment distal to a double ligature placed on the sciatic nerve at intervals 9-15 h and 9-24 h following injection into the dorsal root ganglion of the fifth lumbar root of [35S]methionine and [3H]fucose. After a dose of 100 mg/kg of acrylamide no neurological signs of neuropathy had yet appeared, but retrograde buildup of protein label was significantly reduced for the long interval (2.20 +/- 0.49 arbitrary units (AU) (mean +/- SD) versus 2.81 +/- 0.57 AU in controls, 2p = 0.034). No abnormality of the short interval appeared before a dose of 500 mg/kg was reached. The retrograde transport abnormality was dose-related (r = -0.85, n = 28, and 2p = 1.2 x 10(-8)), as was the degree of neuropathy evaluated by "blind" neurological scoring (r = 0.88, n = 14, and 2p = 2.8 x 10(-5)). After a dose of 500 mg/kg, when the rats were severely disabled with almost total incoordination of the hindlegs, the retrograde accumulation of the long interval was profoundly depressed (1.08 +/- 0.28 AU versus 2.81 +/- 0.57 AU in controls, 2p = 1.2 x 10(-7)). Similar changes were seen in accumulation of glycoprotein label. After the rats had recovered for 4-10 weeks neurological signs of neuropathy had disappeared and the transport abnormality had improved. To test the specificity of acrylamide on the retrograde transport defect N-hydroxymethylacrylamide and methylene-bisacrylamide, which do not induce neuropathy, were studied. None of these related compounds influenced the transport. These observations imply that in acrylamide intoxication a defect in the amount of material carried by retrograde axonal transport rather than in "turnaround" time or in transport velocity is present, that the transport abnormality precedes the development of neuropathy, and that it is related to the degree of the neurological disability. We suggest that the retention of protein in the distal axons in the functional counterpart of the well-known accumulation of vesicular organelles in the preterminals.     

Anterograde Axonal Transport in Rats During Intoxication with Acrylamide

Abstract: Anterograde axonal transport was examined in sensory nerves of rats intoxicated with a low dose (group I) or a high dose (group II) of acrylamide. After injection of either [³⁵S]methionine and [³H]fucose or [³H]proline into the dorsal root ganglia of the 5th lumbar roots, distribution of protein label was measured in 3-mm segments of the sciatic nerve at intervals of 2 h, 4 h, 10 days, and 26 days. No difference in ganglion incorporation was present at 4 h, and the fast transport velocity of methionine label also remained normal [14.7 ± 1.3 mm/h (mean ± SD) in controls versus 14.6 ± 0.3 mm/h and 15.4 ± 1.2 mm/h in acrylamide group I and II, respectively]. Neither was there any decrease in transport velocity of proline label of slow component b (4.18 ± 0.29 mm/day in controls versus 4.29 ± 0.17 mm/d and 4.22 ± 0.29 mm/day in acrylamide group I and II, respectively). In slow component a, however, a significant reduction in the fractional amount of proline label was found (20.8 ± 4.0% in controls versus 17.6 ± 14.9% and 9.7 ± 5.9% in acrylamide group I and II, respectively). Again no decrease in transport velocity was observed (1.03 ± 0.02 mm/day in controls versus 1.06 ± 0.08 mm/day and 1.07 ± 0.03 mm/day in acrylamide group I and II, respectively), and closer inspection of the activity along the nerve did not reveal any alteration in skewness or ‘peakedness’ of the distribution curve. The reduction in amount of protein carried in the slow axonal transport component in rats with severe acrylamide neuropathy (group II) could be associated with fibre breakdown at a late stage of the neuropathic process. The most important consequence of the study is, however, that in contrast to previous suggestions, during acrylamide intoxication no changes are present in protein incorporation or in anterograde axonal transport which can explain the initial pathological or functional abnormalities of the distal axons.     

体外培养过程中许旺细胞S100表达规律研究

目的：目前研究发现,周围神经中许旺细胞的标志物有很多,S100是其中之一。S100在体内表达的变化规律已有比较深入的研究,但是其在体外培养的许旺细胞的表达规律尚不清楚。因此,本课题研究小鼠许旺细胞在体外培养过程中S100蛋白的表达变化规律。方法：取新生（出生5-7 d）C57BL/6小鼠的坐骨神经,酶消化分离获取细胞后,培养纯化扩增3次。用S100免疫荧光法及RT-PCR技术研究许旺细胞在体外培养过程中S100的表达规律。结果：从坐骨神经消化所得到的许旺细胞,早期并不都表达S100,阳性率约为43.48%,随着培养时间延长（培养8天）,所有许旺细胞均表达S100,能够达到阳性率95.66%。结论：体外培养的许旺细胞,其标志物S100阳性率表达随培养时间延长而增加。并且我们发现,S100并不能作为一个可靠的标志物来单独应用鉴定体外培养早期的许旺细胞。     

Identification of Ca2+-Activated Neutral Protease in the Peripheral Nerve and Its Effects on Neurofilament Degeneration

Rat sciatic nerve segments were incubated in five different media. Disappearance of neurofilament (NF) triplet proteins (200K, 160K, and 68K MW) occurred in medium containing Ca²⁺ and was inhibited by the addition of E-64-c or leupeptin. Therefore, the presence in the peripheral nerve of an enzyme whose properties are similar to those of Ca²⁺-activated neutral protease (CANP) is suggested. The extraction of crude CANP from rat sciatic nerve was performed. CANP activity was completely recovered (0.129 ± 0.008 U/g) in the precipitate salted out by the addition of 0 to 50% saturated ammonium sulfate to the soluble fraction of the peripheral nerve (crude CANP). Properties of the crude CANP were examined using NF as a substrate and were found to be similar to those of the CANP extracted from skeletal muscle. Identification of the crude CANP with the CANP extracted from rat skeletal muscle was performed using the immunoreplica method. Bands corresponding to 73K were detected in both CANPs.     

β,β''-Iminodipropionitrile Impairs Retrograde Axonal Transport

beta,beta'-Iminodipropionitrile (IDPN), a neurotoxin, causes redistribution of neurofilaments in axons followed by the development of proximal axonal swellings and, in chronic intoxication, a distal decrease in axonal caliber. The latter changes are caused by a selective impairment in the slow anterograde axonal transport of neurofilament proteins. To assess the role of retrograde axonal transport in IDPN toxicity, we used [3H]N-succinimidyl propionate ([3H]NSP) to label covalently endogenous axonal proteins in sciatic nerve of the rat and measured the accumulation of radioactively labeled proteins in the cell bodies of motor and sensory neurons over time. IDPN was injected intraneurally 6 h or intraperitoneally 1 day before subepineurial injection of [3H]NSP into the sciatic nerve, and the animals were killed 1, 2, and 7 days after [3H]NSP injection. Neurotoxicity was assessed by electron microscopic observation of the nerves of similarly treated animals. Both intraneural and intraperitoneal injection of IDPN caused an acute reduction in the amount of labeled proteins transported back to the cell bodies. The early appearance of these changes suggests that alterations in retrograde transport may play a role in the production of the neuropathic changes.     

Early Stimulation of Phosphatidylcholine Biosynthesis During Wallerian Degeneration of Rat Sciatic Nerve

Phospholipid metabolism was studied in rat sciatic nerve during Wallerian degeneration induced by crush injury. Portions of crushed sciatic nerve, incubated with labeled substrates, showed significantly higher phosphatidylcholine synthesis than normal nerve, prior to any measurable alterations of phospholipid composition. Maximum synthesis occurred 3 days after crush injury, at which time the metabolism of other phospholipids was unchanged. After a rapid decrease in biosynthetic activity, a second phase of enhanced phosphatidylcholine synthesis occurred, beginning 6 days after crush injury. Increased incorporation of [33P]phosphate, [2-3H]glycerol, and [Me-14C]choline indicated stimulation of de novo synthesis of phosphatidylcholine 3 days after injury. Neither base exchange reactions nor sequential methylation of ethanolamine phospholipids contributed significantly to phosphatidylcholine synthesis. Assay of certain key enzymes under optimal conditions in subcellular fractions of sciatic nerve revealed higher activities of cholinephosphate cytidyltransferase, choline phosphotransferase, and acyl-CoA:lysophosphatidylcholine acyltransferase in injured nerve, while choline kinase activity remained unchanged. This indicates that stimulation of phosphatidylcholine synthesis occurs via the cytidine nucleotide pathway, as well as by increased acylation of lysophosphatidylcholine. Although the cause of stimulated phosphatidylcholine synthesis remains unexplained, it is possible that trace amounts of lysophospholipids or other metabolites produced by injury-enhanced phospholipase activity may be responsible.     

Axonal Transport Characteristics of Gangliosides in Sensory Axons of Rat Sciatic Nerve

The distribution of axonally transported gangliosides and glycoproteins along the sciatic nerve was examined from 3 h to 4 weeks following injection of[3H]glucosamine into the fifth lumbar dorsal root ganglion of adult rats. Incorporation of labeled precursor into these glycoconjugates reached a maximal level in the ganglion within 6 h. Outflow patterns of radioactivity for glycoproteins showed a well-defined crest with a transport rate of approximately 330 mm/day. In contrast, the crest of transported gangliosides was continuously attenuated, implying a significant deposition along the axon, and an alternative method of calculating velocity was required. Analysis of accumulation of labeled material at double ligatures demonstrated both anterograde and retrograde transport of glycoproteins and gangliosides and allowed for the calculation of an anterograde transport rate of about 270 mm/day for each. Additional evidence of ganglioside transport is provided in that the TLC pattern of transported radioactive gangliosides accumulating at a ligature is significantly different from the pattern seen in the dorsal root ganglion or following intraneural administration of the labeled precursor. These data indicate that gangliosides are transported at the same rapid rate as glycoproteins but are subject to a more extensive exchange with stationary material than are glycoproteins.     

Changes in Protein Content of Goldfish Optic Nerve During Degeneration and Regeneration Following Nerve Crush

Abstract: After the goldfish optic nerve was crushed, the total amount of protein in the nerve decreased by about 45% within 1 week as the axons degenerated, began to recover between 2 and 5 weeks as axonal regeneration occurred, and had returned to nearly normal by 12 weeks. Corresponding changes in the relative amounts of some individual proteins were investigated by separating the proteins by two-dimensional gel electrophoresis and performing a quantitative analysis of the Coomassie Brilliant Blue staining patterns of the gels. In addition, labelling patterns showing incorporation of [³H]proline into individual proteins were examined to differentiate between locally synthesized proteins (presumably produced mainly by the glial cells) and axonal proteins carried by fast or slow axonal transport. Some prominent nerve proteins, ON1 and ON2 (50–55 kD, pI ～6), decreased to almost undetectable levels and then reappeared with a time course corresponding to the changes in total protein content of the nerve. Similar changes were seen in a protein we have designated NF (～130 kD, pI ～5.2). These three proteins, which were labelled in association with slow axonal transport, may be neurofilament constituents. Large decreases following optic nerve crush were also seen in the relative amounts of α- and β-tubulin, which suggests that they are localized mainly in the optic axons rather than the glial cells. Another group of proteins, W2, W3, and W4 (35–45 kD, pI 6.5–7.0), which showed a somewhat slower time course of disappearance and were intensely labelled in the local synthesis pattern, may be associated with myelin. A small number of proteins increased in relative amount following nerve crush. These included some, P1 and P2 (35–40 kD, pIs 6.1–6.2) and NT (～50 kD, pI ～5.5), that appeared to be synthesized by the glial cells. Increases were also seen in one axonal protein, B (～45 kD, pI ～4.5), that is carried by fast axonal transport, as well as in two axonal proteins, HA1 and HA2 (～60 and 65 kD respectively, pIs 4.5–5.0), that are carried mainly by slow axonal transport. Other proteins, including actin, that showed no net changes in relative amount (but presumably changed in absolute amount in direct proportion to the changes in total protein content of the nerve), are apparently distributed in both the neuronal and nonneuronal compartments of the nerve.     

Identification and functional characterization of thromboxane A2 receptors in Schwann cells

Previous reports have demonstrated the presence of functional thromboxane A2 (TP) receptors in astrocytes and oligodendrocytes. In these experiments, the presence and function of TP receptors in primary rat Schwann cells (rSC) and a neurofibrosarcoma-derived human Schwann cell line (T265) was investigated. Immunocytochemical and immunoblot analyses using polyclonal anti-TP receptor antibodies demonstrate that both cell types express TP receptors. Treatment with the stable thromboxane A2 mimetic U46619 (10 microM) did not stimulate intracellular calcium mobilization in rSC, whereas T265 cells demonstrated a calcium response that was inhibited by prior treatment with TP receptor antagonists. U46619 also stimulated CREB phosphorylation on Ser133 in T265 cells and, to a lesser extent, in rSC. To identify potential mechanisms of CREB phosphorylation in rSC, we monitored intracellular cAMP levels following U46619 stimulation. Elevated levels of cAMP were detected in both rSC (20-fold) and T265 (15-fold) cells. These results demonstrate that TP receptor activation specifically stimulates CREB phosphorylation in T265 cells, possibly by a calcium- and/or cAMP-dependent mechanism. In contrast, TP receptor activation in rSC stimulates increases in cAMP and CREB phosphorylation but does not elicit changes in intracellular calcium.     

Apoptosis Regulates the Number of Schwann Cells at the Premyelinating Stage

Abstract: At the premyelinating stage, the Schwann cells of peripheral nerves are able to recognize the axon, to arrange themselves along it in a nonoverlapping manner, and finally to establish a one-to-one cell-axon relationship. The mechanism that regulates these processes is not known in detail. We found the existence of a significant Schwann cell apoptosis in vivo of rat postnatal sciatic nerve, peaking around postnatal day 3. More than 50% of the neonatal Schwann cells cultured in axon-free medium undergo a rapid apoptosis. The apoptosis can be suppressed by addition of survival factors such as Neu differentiation factors or by increasing the adhesion of Schwann cells to substratum. We suggest that in neonatal nerves in vivo, Schwann cells are highly susceptible to apoptosis, but they are saved from death by contact with axons. The dramatic increase in number of Schwann cells between postnatal day 0 and 3 overcomes the number of axons available for them. Consequently the Schwann cells that fail to contact an axon undergo apoptosis. In conclusion, the number of Schwann cells in the developing nerves is regulated by the apoptosis and clearly depends on the survival signals from axons.     

Inhibition of transient receptor potential melastatin 7 (TRPM7) protects against Schwann cell trans-dedifferentiation and proliferation during Wallerian degeneration

ABSTRACT

Irreversible peripheral neurodegenerative diseases such as diabetic peripheral neuropathy are becoming increasingly common due to rising rates of diabetes mellitus; however, no effective therapeutic treatments have been developed. One of main causes of irreversible peripheral neurodegenerative diseases is dysfunction in Schwann cells, which are neuroglia unique to the peripheral nervous system (PNS). Because homeostasis of calcium (Ca²⁺) and magnesium (Mg²⁺) is essential for Schwann cell dynamics, the regulation of these cations is important for controlling peripheral nerve degeneration and regeneration. Transient receptor potential melastatin 7 (TRPM7) is a non-selective ion (Ca²⁺ and Mg²⁺) channel that is expressed in Schwann cells. In the present study, we demonstrated in an ex vivo culture system that inhibition of TRPM7 during peripheral nerve degeneration (Wallerian degeneration) suppressed dedifferentiable or degenerative features (trans-dedifferentiation and proliferation) and conserved a differentiable feature of Schwann cells. Our results indicate that TRPM7 could be very useful as a molecular target for irreversible peripheral neurodegenerative diseases, facilitating discovery of new therapeutic methods for improving human health.     

Peripheral Nerve Phospholipid Composition: Development in Normal Nerve and Age-Dependent Changes in Wallerian Degenerated Nerve

Abstract: The phospholipid composition of normal peripheral nerve as a function of developmental age as well as that of Wallerian-degenerated nerve as a function of age at nerve transection and duration of Wallerian degeneration have been quantitated in rabbit sciatic nerve. During development, increases in the proportions of ethanolamine plasmalogen, sphingomyelin, and combined phosphatidyl serine plus phosphatidyl inositol and decreases in the proportions of phosphatidyl choline and phosphatidyl ethanolamine correlated well with the concurrent myelin accretion. During Wallerian degeneration, age-dependent changes in phospholipid composition were observed. The large and statistically significant increase in the proportion of phosphatidyl choline and decrease in the proportion of ethanolamine plasmalogen were manifest promptly in nerves transected at 2 weeks of age but in a delayed manner in nerves transected at 8, 12, and 20 weeks of age. The rate of loss of individual phospholipids was greater in nerves transected at younger ages. The findings from normal developing peripheral nerve may well serve as baseline data for subsequent studies of phospholipid composition in pathological peripheral nerve. The Findings from Wallerian-degenerated peripheral nerve provide additional evidence for age-dependent chemical changes occurring in Wallerian-degenerated peripheral nerve that may be of significance in explaining the superior functional recovery from peripheral nerve injury observed in younger compared with older subjects.     

Changes in Rapid Transport of Phospholipids in the Rat Sciatic Nerve During Axonal Regeneration

Abstract: Axonal transport of phospholipids in normal and regenerating sciatic nerve of the rat was studied. At various intervals after axotomy of the right sciatic nerve in the midthigh region and subsequent perineurial sutures of the transected fascicles, a mixture of 60 μCi [Me-^HC]choline and 15 μCi [2-³H]glycerol in the region of the spinal motor neurons of the L5 and L6 segments was injected bilaterally. The amount of radioactive lipid (and in certain cases its distribution in various lipid classes) along the nerve was determined as a function of time. Three days after fascicular suture and 6 h after spinal cord injection of precursors, there was an accumulation of labeled phospholipids and sphingolipids in the transected sciatic nerve in the region immediately proximal to the site of suture. Nine days after, there was a marked increase in the accumulation of radioactivity in the distal segments of the injured nerve, which increased up to 14 days after cutting and disappeared as regeneration proceeded (21–45 days). In all segments of both normal and regenerating nerve fibers, as well as in L5 and L6 spinal cord segments, only phosphatidylcholine and sphingomyelin were labeled with [¹⁴C]choline. These results suggest that the regeneration process in a distal segment of a peripheral neuron, following cutting and fascicular repairing by surgical sutures, is sustained in the first 3 weeks by changes in the amount of phospholipids rapidly transported along the axon towards the site of nerve fiber outgrowth.     

Uptake and Anterograde Axonal Transport of Aleuria Lectin in Retinal Ganglion Cells of the Rabbit

A fucose-specific lectin from Aleuria aurantia was used to study the dynamics of neuronal membrane glycoproteins. Albino rabbits received vitreal injections of affinity-purified 125I-Aleuria lectin. The radioactive probe was internalized by adsorptive endocytosis into retinal ganglion cells, and transported intact down to the nerve terminals in the contralateral geniculate bodies and superior colliculi. We found that the radiolabeled lectin was transported with at least two distinct rates (I, approximately 205 mm/day; II, approximately 45 mm/day) corresponding to the two rapid phases of anterograde transport of endogenous polypeptides described earlier in this system. This is the first evidence that an exogenous macromolecule may be transported along the axon at more than one velocity.     

Ganglioside Treatment of Streptozotocin-Diabetic Rats Prevents Defective Axonal Transport of 6-Phosphofructokinase Activity

This study measured axonal transport of 6-phosphofructokinase (PFK) and aldolase activities in the sciatic nerves of rats with short-term streptozotocin-induced diabetes. The diabetic rats showed deficits in anterograde (69% of controls; p less than 0.001) and retrograde (33% of controls; p less than 0.01) accumulations of PFK activity as well as its content per unit length of unconstricted sciatic nerve (86% of controls; p less than 0.05). There were no accumulation deficits in aldolase activity in the nerves of the diabetic rats, although the activity per unit length of unconstricted nerve was deficient (81% of controls; p less than 0.05). Treatment of diabetic rats with mixed bovine brain gangliosides (10 mg/kg of body weight/day, i.p.) did not affect the deficit in PFK activity in unconstricted nerve (84% of ganglioside-treated controls; p less than 0.01), but all the other defects in enzyme activities were prevented completely. The diabetic rats also showed a reduction of 7% (p less than 0.01) in sciatic nerve dry weight per unit length, which was prevented by ganglioside treatment. In contrast, the reduced motor nerve conduction velocity, accumulation of polyol pathway metabolites, and depletion of myo-inositol, characteristic of untreated short-term diabetes, were unaffected by ganglioside treatment.     

Retrograde Axonal Transport of Gangliosides and Glycoproteins in the Motoneurons of Rat Sciatic Nerve

Axonal transport of glycoconjugates was studied in the motoneurons of rat sciatic nerve following injection of [3H]glucosamine into the lumbosacral spinal cord. After varying time intervals, the sciatic nerve was exposed, and two ligatures were tied for collection of materials undergoing anterograde and retrograde transport. Gangliosides and glycoproteins were found to undergo fast anterograde transport, estimated at 284-446 mm/day. Both classes underwent retrograde transport as well, with labeled glycoproteins returning slightly ahead of labeled gangliosides. Only minor quantities of labeled proteoglycans were detected. Purified gangliosides extracted from nerve segments were fractionated according to sialic acid number on diethylaminoethyl-Sephadex; the distributional pattern tended to resemble that of brain gangliosides. The similarity between anterograde and retrograde patterns suggested absence of metabolic changes in gangliosides entering and leaving the axon-nerve terminal structures.     

Identification of G Protein Subtypes in Peripheral Nerve and Cultured Schwann Cells

In this study, we investigated the expression of various G proteins in whole sciatic nerves, in myelin and nonmyelin fractions from these nerves, and in membranes of immortalized Schwann cells. In myelin, nonmyelin, and Schwann cell membranes we detected two 39-40-kDa pertussis toxin substrates that were resolved on separation on urea-gradient gels. Two cholera toxin substrates with apparent molecular masses of 42 and 47 kDa were present in nerve and brain myelin and in Schwann cell membranes. In these membranes, a third 45-kDa cholera toxin substrate, which displayed the highest labeling, was also present. Immunoblotting with specific antisera allowed the identification of G(o) alpha, Gi1 alpha, Gi2 alpha, Gi3 alpha, Gq/G11 alpha, and the two isoforms of Gs alpha in nerve homogenates, nerve, and brain myelin fractions. In Schwann cell membranes we identified G(o) alpha, Gi2 alpha, Gi3 alpha, and proteins from the Gq family, but no immunoreactivity toward anti-Gi1 alpha antiserum was detected. In these membranes, anti-Gs alpha antibody recognized the three cholera toxin substrates mentioned above, with the 45-kDa band displaying the highest immunoreactivity. Relative to sciatic nerve myelin, the Schwann cell membranes revealed a significantly higher expression of Gi3 alpha and the absence of Gi1 alpha. The different distribution of G proteins among the different nerve compartments might reflect the very specialized function of Schwann cells and myelin within the nerve.