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Query: UMLS:C0344329 (collapse)
 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The semaphorins are a large protein family that is involved in the patterning of neuronal connections in the developing nervous system of both vertebrates and invertebrates. The chemorepulsive axon guidance signal Semaphorin 3A (Sema3A) induces the depolymerization of actin filaments and the collapse of sensory growth cones by activating a receptor complex that contains a plexin as the signal-transducing subunit. Here we show that, of a large number of GTPases tested, only Rnd1 and RhoD bind the cytoplasmic domain of Plexin-A1. Recruitment of active Rnd1 is sufficient to trigger signaling by Plexin-A1, even in the absence of Sema3A, and initiates cytoskeletal collapse by activating its cytoplasmic domain. RhoD, in contrast, blocks Plexin-A1 activation by Rnd1 and repulsion of sympathetic axons by Sema3A. Thus, the antagonism of two GTPases regulates the activity of the Sema3A receptor, and activation by Rnd1 appears to be an essential step in signaling by Plexin-A1.
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PMID:Antagonistic effects of Rnd1 and RhoD GTPases regulate receptor activity in Semaphorin 3A-induced cytoskeletal collapse. 1178 92

Plexins are receptors for the axon guidance molecule semaphorins, and several lines of evidence suggest that Rho family small GTPases are implicated in the downstream signaling of Plexins. Recent studies have demonstrated that Plexin-B1 activates RhoA and induces growth cone collapse through Rho-specific guanine nucleotide exchange factor PDZ-RhoGEF. Here we show that Rnd1, a member of Rho family GTPases, directly interacted with the cytoplasmic domain of Plexin-B1. In COS-7 cells, coexpression of Rnd1 and Plexin-B1 induced cell contraction in response to semaphorin 4D (Sema4D), a ligand for Plexin-B1, whereas expression of Plexin-B1 alone or coexpression of Rnd1 and a Rnd1 interaction-defective mutant of Plexin-B1 did not. The Sema4D-induced contraction in Plexin-B1/Rnd1-expressing COS-7 cells was suppressed by dominant negative RhoA, a Rho-associated kinase inhibitor, a dominant negative form of PDZ-RhoGEF, or deletion of the carboxyl-terminal PDZ-RhoGEF-binding region of Plexin-B1, indicating that the PDZ-RhoGEF/RhoA/Rho-associated kinase pathway is involved in this morphological effect. We also found that Rnd1 promoted the interaction between Plexin-B1 and PDZ-RhoGEF and thereby dramatically potentiated the Plexin-B1-mediated RhoA activation. We propose that Rnd1 plays an important role in the regulation of Plexin-B1 signaling, leading to Rho activation during axon guidance and cell migration.
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PMID:Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells. 1273 Feb 35

Plexins are cell surface receptors for semaphorin molecules, and their interaction governs cell adhesion and migration in a variety of tissues. We report that the Semaphorin 4D (Sema4D) receptor Plexin-B1 directly stimulates the intrinsic guanosine triphosphatase (GTPase) activity of R-Ras, a member of the Ras superfamily of small GTP-binding proteins that has been implicated in promoting cell adhesion and neurite outgrowth. This activity required the interaction of Plexin-B1 with Rnd1, a small GTP-binding protein of the Rho family. Down-regulation of R-Ras activity by the Plexin-B1-Rnd1 complex was essential for the Sema4D-induced growth cone collapse in hippocampal neurons. Thus, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras.
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PMID:The Semaphorin 4D receptor Plexin-B1 is a GTPase activating protein for R-Ras. 1529 73

Plexins serve as receptors for repulsive axonal guidance molecules semaphorins. The cytoplasmic domain of the semaphorin 4D (Sema4D) receptor, Plexin-B1 has two separated Ras GTPase-activating protein (GAP)-homologous domains, C1 and C2. Recently, we reported that the Rho family small GTPase Rnd1 associates with Plexin-B1, and the Plexin-B1-Rnd1 complex stimulates GTPase activity of R-Ras, inducing growth cone collapse in hippocampal neurons in response to Sema4D. However, the molecular mechanisms by which Plexin-B1 exhibits the GAP activity remain unclear. In this report, critical roles of Rnd1 and Sema4D in Plexin-B1-stimulated R-Ras GAP activity and neurite remodeling were examined. The N-terminal region of the cytoplasmic domain of Plexin-B1 containing the C1 domain interacts with the C-terminal region containing the C2 domain, and Rnd1 disrupts this interaction. On the other hand, Sema4D induces clustering of Rnd1-bound Plexin-B1, in parallel with inactivation of R-Ras in cells. Antibody clustering of the recombinant cytoplasmic domain of Plexin-B1 in the presence of Rnd1 triggers the R-Ras GAP activity. Deletion of the extracellular domain of Plexin-B1 causes ligand-independent clustering of the receptor, rendering the receptor constitutively active in the presence of Rnd1, and induces contraction of COS-7 cells and inhibition of neurite outgrowth in hippocampal neurons. These results indicate that Rnd1 opens the two R-Ras GAP domains of Plexin-B1, and Sema4D-induced receptor clustering stimulates R-Ras GAP activity and neurite remodeling in hippocampal neurons.
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PMID:Molecular dissection of the semaphorin 4D receptor plexin-B1-stimulated R-Ras GTPase-activating protein activity and neurite remodeling in hippocampal neurons. 1560 54

Semaphorins are a family of secreted and membrane-bound proteins known as axonal pathfinders. Sema4A, a member of class 4 semaphorins, induces growth cone collapse of hippocampal neurons. The binding of Sema4A to growth cones indicates the presence of receptors transmitting signals through the intracellular effectors to induce growth cone collapse in hippocampal neurons. Transfection experiments of the candidate receptor genes into COS-7 cells demonstrated that Sema4A binds to axonal guidance receptors Plexin-B1, -B2 and -B3. To identify the functional Sema4A receptor and the signal transduction machinery, COS-7 cell contraction assay was performed, in which intracellular signal transmission induced by Sema4A triggered cell contraction. Expression vectors encoding plexins and Rnd1, a Rho family GTPase, were transfected into COS-7 cells, and a proportion of contracted cells among the transfectants was determined after incubation with Sema4A. The results demonstrated that the combination of Rnd1 and Plexin-B1, -B2 or -B3 induced significant cell contraction, indicating that B-type plexins transmit an intracellular signal of Sema4A through Rnd1. To further study the mechanism of B-type plexin-mediated signaling in Sema4A-induced growth cone collapse, mouse hippocampal neurons transfected with a control or expression plasmid encoding a constitutively active mutant of R-Ras (R-RasQL) were stimulated with Sema4A, followed by the assessment of growth cone collapse. Expression of R-RasQL significantly blocked Sema4A-induced growth cone collapse in the hippocampal neurons compared with the control plasmid. Sema4A thus induces growth cone collapse through the down-regulation of R-Ras activity in mouse hippocampal neurons.
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PMID:Sema4A induces cell morphological changes through B-type plexin-mediated signaling. 2004 31

Plexins are cell surface receptors that bind to semaphorins and transduce signals that regulate neuronal development, immune responses, and other processes. Signaling through plexins has been proposed to rely on specific guanosine triphosphatase (GTPase)-activating protein (GAP) activity for R-Ras and M-Ras. Activation of this GAP activity of plexins appears to require simultaneous binding of semaphorin to the plexin extracellular domain and of the Rho GTPases Rac1 or Rnd1 to the cytoplasmic region. However, GAP activity of plexins has eluded detection in several recent studies. We show that the purified cytoplasmic region of plexin uses a noncanonical catalytic mechanism to act as a GAP for Rap, but not for R-Ras or M-Ras. The RapGAP activity of plexins was autoinhibited and was activated by induced dimerization. Biochemical and crystallographic analyses demonstrated that binding of Rho GTPases did not directly contribute to activation of plexin RapGAP activity. Semaphorin stimulated the RapGAP activity of full-length plexin in cells, which was required for plexin-mediated neuronal growth cone collapse. Together, these findings define a pathway for plexin signaling and provide insights into the mechanism for semaphorin-induced activation of plexins.
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PMID:Plexins are GTPase-activating proteins for Rap and are activated by induced dimerization. 2225 63

Rnd proteins comprise a branch of the Rho family of small GTP-binding proteins, which have been implicated in rearrangements of the actin cytoskeleton and microtubule dynamics. Particularly in the nervous system, Rnd family proteins regulate neurite formation, dendrite development and axonal branching. A secreted form of the co-chaperone Stress-Inducible Protein 1 (STI1) has been described as a prion protein partner that is involved in several processes of the nervous system, such as neurite outgrowth, neuroprotection, astrocyte development, and the self-renewal of neural progenitor cells. We show that cytoplasmic STI1 directly interacts with the GTPase Rnd1. This interaction is specific for the Rnd1 member of the Rnd family. In the COS collapse assay, overexpression of STI1 prevents Rnd1-plexin-A1-mediated cytoskeleton retraction. In PC-12 cells, overexpression of STI1 enhances neurite outgrowth in cellular processes initially established by Rnd1. Therefore, we propose that STI1 participates in Rnd1-induced signal transduction pathways that are involved in the dynamics of the actin cytoskeleton.
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PMID:STI1 antagonizes cytoskeleton collapse mediated by small GTPase Rnd1 and regulates neurite growth. 2469 Feb 81