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The CRMP Family of Proteins and Their Role in Sema3A Signaling

  • Eric F. Schmidt
  • Stephen M. Strittmatter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 600)

Abstract

The CRMP proteins were originally identified as mediators of Sema3A signaling and neuronal differentiation. Much has been learned about the mechanism by which CRMPs regulate cellular responses to Sema3A. In this review, the evidence for CRMP as a component of the Sema3A signaling cascade and the modulation of CRMP by plexin and phosphorylation are considered. In addition, current knowledge of the function of CRMP in a variety of cellular processes, including regulation of the cytoskeleton and endocytosis, is discussed in relationship to the mechanisms of axonal growth cone Sema3A response

The secreted protein Sema3A (collapsin-1) was the first identified vertebrate semaphorin. Sema3A acts primarily as a repulsive axon guidance cue, and can cause a dramatic collapse of the growth cone lamellipodium. This process results from the redistribution of the F-actin cytoskeleton1,2 and endocytosis of the growth cone cell membrane.2, 3, 4 Neuropilin-1 (NP1) and members of the class A plexins (PlexA) form a Sema3A receptor complex, with NP1 serving as a high-affinity ligand binding partner, and PlexA transducing the signal into the cell via its large intracellular domain. Although the effect of Sema3A on growth cones was first described nearly 15 years ago, the intracellular signaling pathways that lead to the cellular effects have only recently begun to be understood. Monomeric G-proteins, various kinases, the redox protein, MICAL, and protein turnover have all been implicated in PlexA transduction. In addition, the collapsin-response-mediator protein (CRMP), family of cytosolic phosphoproteins plays a crucial role in Sema3A/NP1/PlexA signal transduction. Current knowledge regarding CRMP functions are reviewed here

Keywords

Growth Cone Optic Neuritis Paraneoplastic Neurological Syndrome Nonneuronal Cell Growth Cone Collapse 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Eric F. Schmidt
  • Stephen M. Strittmatter
    • 1
  1. 1.Stephen M. Strittmatter—Department of NeurologyYale University School of MedicineNew HavenUSA

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