How important are Rho GTPases in neurosecretion?

Rho GTPases are small GTP binding proteins belonging to the Ras superfamily which act as molecular switches that regulate many cellular function including cell morphology, cell to cell interaction, cell migration and adhesion. In neuronal cells, Rho GTPases have been proposed to regulate neuronal development and synaptic plasticity. However, the role of Rho GTPases in neurosecretion is poorly documented. In this review, we discuss data that highlight the importance of Rho GTPases and their regulators into the control of neurotransmitter and hormone release in neurons and neuroendocrine cells, respectively.     

Rho蛋白

常见的异源三聚体ＧＴＰ结合蛋白 ,是通过其 (亚基在无活性的ＧＤＰ结合状态和有活性的ＧＴＰ结合状态之间的转换来完成对膜相关受体传来的信号反应 ,而与之同样起“分子开关”作用的另一类小分子Ｇ蛋白 (ｓｍａｌｌＧｐｒｏｔｅｉｎ ,又称ＧＴＰａｓｅ ,即ＧＴＰ酶 ) ,它们的激活不是直接通过与激动型的Ｇ蛋白偶联受体 (Ｇｐｒｏｔｅｉｎ ｃｏｕｐｌｅｄｒｅｃｅｐｔｏｒ,ＧＰＣＲ)相互作用而调节其活性 ,而是通过鸟嘌呤核苷交换因子(ｇｕａｎｉｎｅｎｕｃｌｅｏｔｉｄｅｅｘｃｈａｎｇｅｆａｃｔｏｒ,ＧＥＦ)来控制这类小分子Ｇ蛋白的ＧＴ…     

Rho protein crosstalk: another social network?

Many fundamental processes in cell biology are regulated by Rho GTPases, including cell adhesion, migration and differentiation. While regulating cellular functions, members of the Rho protein family cooperate or antagonize each other. The resulting molecular network exhibits many levels of interaction dynamically regulated in time and space. In the first part of this review we describe the main mechanisms of this crosstalk, which can occur at three different levels of the pathway: (i) through regulation of activity, (ii) through regulation of protein expression and stability, and (iii) through regulation of downstream signaling pathways. In the second part we illustrate the importance of Rho protein crosstalk with two examples: integrin-based adhesion and cell migration.     

Rho/Rho激酶信号通路与脉管收缩

Rho/Rho激酶信号通路在正常血管、淋巴管等脉管收缩过程中发挥重要的调节作用,并参与休克后血管反应性和钙敏感性的双相调节以及休克淋巴管低反应性的发生.以Rho/Rho激酶为靶点,对于干预休克脉管系统低反应性的发生具有重要意义.本文综述Rho/Rho激酶信号通路在脉管收缩中的调节机制.     

"Contractile interstitial cells" in pulmonary alveolar septa: a possible regulator of ventilation-perfusion ratio? Ultrastructural, immunofluorescence, and in vitro studies

In the lungs of healthy rats, humans, lambs, and monkeys, about 50% of the alveolar interstitial cells—resembling fibroblasts—contain bundles of fibrils measuring 30–80 Å in diameter. Immunofluorescence studies on frozen sections of rat lung demonstrate that many interstitial cells bind sera containing antiactin antibodies. On account of these two sets of findings and our additional in vitro studies suggesting alveolar tissue contraction due to hypoxia or epinephrine, we postulate that the alveolar septa contain contractile cells different from that of smooth muscle. For these cells we propose the name of "contractile interstitial cells." Such cells lie within the thick portion of the air-blood barrier and around the pre- or postcapillary vessels. Hence it is possible that they play a role in the autoregulation of ventilation/perfusion (V/Q) ratio, particularly in hypoxic pulmonary hypertension. These findings, demonstrating a contractile system other than bronchial and arterial smooth muscle, suggest that the alveolus should no more be conceived as a passive "organ."     

Koffka, Köhler, and the "crisis" in psychology

This paper examines the claims of the Gestalt psychologists that there was a crisis in experimental psychology ca. 1900, which arose because the prevailing sensory atomism excluded meaning from among psychological phenomena. The Gestaltists claim that a primary motivation of their movement was to show, against the speculative psychologists and philosophers and Verstehen historians, that natural scientific psychology can handle meaning. Purportedly, they revealed this motivation in their initial German-language presentations but in English emphasized their scientific accomplishments for an American audience. The paper finds that: there was a recognized crisis in the new experimental psychology ca. 1900 pertaining especially to sensory atomism; that the Gestaltists responded to the crisis with new experimental findings and theoretical concepts (Gestalten) that challenged atomism; in both languages, they raised problems of meaning and discussed the contest with speculative psychology and philosophy only after presenting their scientific case; that they introduced phenomenological observations on meaning and perceptual organization into their psychology but did not develop a theory of meaning or solve philosophical problems; that they argued "philosophically," that is, using abstract, conceptual arguments; and that this aspect of their cognitive style was not received well by some prominent members of their American audience.     

Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility

Higher vertebrates have 3 Rho GTPases, RhoA, RhoB, and RhoC, which share 85% amino acid sequence identity. Here, we compare and contrast the roles of RhoA, B, and C in the regulation of the cytoskeleton and cell motility. Despite their similarity, some regulators and effectors show preferential interaction with RhoA, B, or C, and the three proteins show differences in function in cells. RhoA plays a key role in the regulation of actomyosin contractility. RhoB, which is localized primarily on endosomes, has been shown to regulate cytokine trafficking and cell survival, while RhoC may be more important in cell locomotion. In cancer cells, the expression and activity of RhoA, B, and C is altered in different ways. Together, this evidence suggests that although the 3 isoforms of Rho are structurally highly homologous, they have different cellular functions.     

Male "mixed" reproductive strategies in biparental species: Trivers was probably right, but why?

Trivers proposed that, if parental care by both sexes is advantageous, males should practice a "mixed" strategy of seeking extrapair copulations, while restricting their parental investment to offspring of social mates. We explore circumstances under which males should limit their parental care in the predicted manner. We find that Trivers's "mixed" strategy will generally be evolutionarily stable so long as either socially monogamous or polygynous males usually sire more offspring per brood from a social mate than they typically sire in broods of extrapair mates. Polygynous males should spread investment across their home nests unless the expected number of chicks sired in them differs widely. Whether polygynous males should restrict paternal care to social mates' offspring hinges additionally on resident male investment in broods containing extrapair young: if resident males contribute minimally, some investment by a polygynous extrapair male becomes more advantageous. Recently reviewed data on extrapair fertilization distributions within monogamous and polygynous passerines suggest that extrapair offspring often predominate numerically within their broods, consistent with sperm expenditure theory. Nevertheless, most species conform to the model's criterion regarding relative parentage levels in broods of social versus extrapair mates. Patterns of extrapair parentage thus appear sufficient to stabilize biparental care systems.     

Rho GTPases与肿瘤

Rho GTPases参与调控细胞的多种关键生物学行为,特别是细胞的生长、细胞骨架的形成、转录调节等生物学过程. 在肿瘤的发生发展中Rho GTPases也扮演了重要的角色．本文将回顾Rho GTPases的调控（包括经典及非经典调控方式）及其关键成员（RhoA、Cdc42及Rac1）与临床肿瘤的研究进展,特别是它们参与调控肿瘤的增殖、迁移、侵袭、凋亡等恶性生物学行为,从而为研发靶向Rho GTPases的小分子/基因药物了奠定基础．     

Bacterial virulence factors targeting Rho GTPases: parasitism or symbiosis?

In the past few years, an important question in microbiology has arisen from reports indicating that several pathogenic bacteria have evolved virulence factors directed towards a Ras subfamily of GTPases, namely the Rho GTPases. Progress made in studying both the virulence factors and the signaling pathways involving Rho GTPases has shed light on this crosstalk. One central question is raised by the findings that both activating and inactivating virulence factors that target Rho GTPases coexist in some pathogenic bacteria. Further studies on this peculiar aspect of the bacteria-host cell interactions, which leads to the outbreak of infectious diseases, might clarify whether this aspect of Rho GTPase activation or inactivation represents a finely adapted response of the pathogen for its own benefit or might lead to a reaction of the host against the bacteria.     

Rho GTPases and exocytosis: what are the molecular links?

Delivery of proteins or lipids to the plasma membrane or into the extracellular space occurs through exocytosis, a process that requires tethering, docking, priming and fusion of vesicles, as well as F-actin rearrangements in response to specific extracellular cues. GTPases of the Rho family have been implicated as important regulators of exocytosis, but how Rho proteins control this process is an open question. In this review, we focus on molecular connections that drive Rho-dependent exocytosis in polarized and regulated exocytosis. Specifically, we present data showing that Rho proteins interaction with the exocyst complex and IQGAP mediates polarized exocytosis, whereas interaction with actin-binding proteins like N-WASP mediates regulated exocytosis.     

Rho GTPases和细胞凋亡

细胞凋亡涉及细胞骨架的形态学改变,Rho GTPases在细胞骨架改变中起着至关重要的作用。近年来的研究揭示了Rho蛋白家族在肌动蛋白(actin)聚合、解聚及actin-myosin的分子调节机制。同时越来越多的研究表明,Rho GTPases在巨噬细胞吞噬凋亡小体中也发挥了关键作用。本综述就Rho GTPases信号途径在细胞凋亡中细胞骨架的结构改变及凋亡小体被吞噬过程中的作用进行具体讨论。