The molecules of memory

Identifying the key components in the molecular mechanisms of learning and memory is a highly complex process. Here we look at some specific experimental research that has contributed to our knowledge of molecular memory.     

Signaling within a caveolae-like membrane microdomain in human neuroblastoma cells in response to fibroblast growth factor

It is now clear that the plasma membrane is not homogeneous but contains specific subcompartments characterized by their unique lipid and protein composition. Based on their enrichment in various signaling molecules, these microcompartments are now recognized to be sites of localized signal transduction for several extracellular stimuli. At least two different types of microdomains can be identified, largely based on the presence or absence of the caveolin proteins. The generic name of caveolae-like domains is commonly used to refer to both domains indistinguishably. Although caveolin proteins were long thought to be absent from the brain, we have shown that the human neuroblastoma cell line LAN-1 expresses both caveolin-1 and caveolin-2. Basic fibroblast growth factor (FGF)-2 induced a specific signaling response within the caveolae-like domain of LAN-1 cells, characterized by the tyrosine phosphorylation of a 75-80-kDa protein. This protein present in the caveolae-like domains has properties suggesting that it is a member of the SNT family of adapter proteins. The signaling event originating in the caveolae-like domains in response to FGF-2 appeared to require the activation of at least Fyn and Lyn, two members of the Src family of tyrosine kinases. This work suggests that compartmentalized signaling within caveolae-like domains may create a level of specificity for certain growth factors such as FGF.     

Purification and characterization of barley dipeptidyl peptidase IV

Barley (Hordeum vulgare L.) storage proteins, which have a high content of proline (Pro) and glutamine, are cleaved by cysteine endoproteases to yield peptides with a Pro next to the N-terminal and/or C-terminal amino acid residues. A peptidase cleaving after Xaa-Pro- at the N terminus of peptides was purified from green barley malt. It was identified as a serine-type dipeptidyl peptidase (DPP), based on inhibitor studies, and the nature of the cleavage product. It is a monomeric glycoprotein with an apparent molecular mass of 105 kD (85 kD after deglycosylation), with a pI of 3.55 and a pH optimum at 7.2. Substrate specificity was determined with a series of fluorogenic peptide substrates with the general formula Xaa-Pro-AMC, where Xaa is an unspecified amino acid and AMC is 7-amino-4-methylcoumarin. The best substrates were Xaa = lysine and arginine, while the poorest were Xaa = aspartic acid, phenylalanine, and glutamic acid. The K(m) values ranged from 0.071 to 8.9 microM, compared with values of 9 to 130 microM reported for mammalian DPP IVs. We discuss the possible role of DPP IV in the degradation of small Pro-containing peptides transported from the endosperm to the embryo of the germinating barley grain.     

Weight loss increases cardiovagal baroreflex function in obese young and older men

We tested the hypothesis that reductions in total body and abdominal visceral fat with energy restriction would be associated with increases in cardiovagal baroreflex sensitivity (BRS) in overweight/obese older men. To address this, overweight/obese (25 < or = body mass index < or = 35 kg/m(2)) young (OB-Y, n = 10, age = 32.9 +/- 2.3 yr) and older (OB-O, n = 6, age = 60 +/- 2.7 yr) men underwent 3 mo of energy restriction at a level designed to reduce body weight by 5-10%. Cardiovagal BRS (modified Oxford technique), body composition (dual-energy X-ray absorptiometry), and abdominal fat distribution (computed tomography) were measured in the overweight/obese men before weight loss and after 4 wk of weight stability at their reduced weight and compared with a group of nonobese young men (NO-Y, n = 13, age = 21.1 +/- 1.0 yr). Before weight loss, cardiovagal BRS was approximately 35% and approximately 60% lower (P < 0.05) in the OB-Y and OB-O compared with NO-Y. Body weight (-7.8 +/- 1.1 vs. -7.3 +/- 0.7 kg), total fat mass (-4.1 +/- 1.0 vs. -4.4 +/- 0.8 kg), and abdominal visceral fat (-27.6 +/- 6.9 vs. -43.5 +/- 10.1 cm(2)) were reduced (all P < 0.05) after weight loss, but the magnitude of reduction did not differ (all P > 0.05) between OB-Y and OB-O, respectively. Cardiovagal BRS increased (11.5 +/- 1.9 vs. 18.5 +/- 2.6 ms/mmHg and 6.7 +/- 1.2 vs. 12.8 +/- 4.2 ms/mmHg) after weight loss (both P < 0.05) in OB-Y and OB-O, respectively. After weight loss, cardiovagal BRS in the obese/overweight young and older men was approximately 105% and approximately 73% (P > 0.05) of NO-Y (17.5 +/- 2.2 ms/mmHg). Therefore, the results of this study indicate that weight loss increases the sensitivity of the cardiovagal baroreflex in overweight/obese young and older men.     

The influence of "host release factor" on carbon release by zooxanthellae isolated from fed and starved Aiptasia pallida (Verrill).

Symbiotic dinoflagellates (zooxanthellae) typically respond to extracts of host tissue with enhanced release of short-term photosynthetic products. We examined this "host release factor" (HRF) response using freshly isolated zooxanthellae of differing nutritional status. The nutritional status was manipulated by either feeding or starving the sea anemone Aiptasia pallida (Verrill). The release of fixed carbon from isolated zooxanthellae was measured using 14C in 30 min experiments. Zooxanthellae in filtered seawater alone released approximately 5% of photosynthate irrespective of host feeding history. When we used a 10-kDa ultrafiltrate of A. pallida host tissue as a source of HRF, approximately 14% of photosynthate was released to the medium. This increased to over 25% for zooxanthellae from anemones starved for 29 days or more. The cell-specific photosynthetic rate declined with starvation in these filtrate experiments, but the decline was offset by the increased percentage release. Indeed, the total amount of released photosynthate remained unchanged, or even increased, as zooxanthellae became more nutrient deficient. Similar trends were also observed when zooxanthellae from A. pallida were incubated in a 3-kDa ultrafiltrate of the coral Montastraea annularis, suggesting that HRF in the different filtrates operated in a similar manner. Our results support the suggestion that HRF diverts surplus carbon away from storage compounds to translocated compounds such as glycerol.     

Population biology of salt marsh and sand dune annuals

Annuals represent a significant component of the vegetation of coastal salt marshes and sand dunes. From many points of view, the two habitats might appear to have little in common. Yet both are characterized by episodes of low water potential, marked spatial and temporal heterogeneity and a zonation which, within certain limits, reflects successional change.There are also similarities of distribution. Annuals are dominant usually in the pioneer stages; the Salicornia-dominated low marsh areas are perhaps analogues with strandline ephemeral populations (e.g. Cakile maritima) on the fore-dunes. In mature stages, annuals are associated with small gaps in the matrix of perennials, at least some of these arising from drought or disturbance. Nevertheless populations can reach very high densities.The most striking contrast is phenological; only summer annuals are found on marshes, whereas winter annuals predominate on dunes (except for the strandline). Similarly there is a difference in species richness. Rather few species of annual are typical of marshes while a great many are found on dunes.Properties of the seed bank, survival, reproduction and population regulation are compared in marsh and dune annuals, with special reference to Cakile, Salicornia, Rhinanthus and Vulpia. Interpretations are suggested which take account of environmental predictability and heterogeneity. Finally, the general applicability of simple mathematical models of these populations in the different coastal habitats is considered.Nomenclature follows Clapham, Tutin & Warburg (1981) except where otherwise stated.