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Phosphorylation and cleavage of the family of collapsin response mediator proteins may play a central role in neurodegeneration after CNS trauma.

Abstract
The family of the collapsin response mediator proteins (CRMPs) plays a significant physiological role in neuronal cell bodies and axons within the integrated mammalian central nervous system (CNS). Trauma-induced damage to the CNS results in variable degrees of axonal degeneration, and this may lead to neuronal cell death in key grey matter regions. Site-specific phosphorylation of certain CRMPs has been associated with trauma-induced axonal degeneration. Moreover, recent data implicate the pro-apoptotic, calcium-dependent protease calpain as a key initiator of CRMP cleavage. The primary cleavage product of injury-induced neuronal calpain activation is a C-terminus truncated 55- to 58-kDa form of CRMP, which may exert its effects within the cytoplasm and axonal core, or alternatively through its translocation into the nucleus, initiating neuronal cell death. The precise structure of cleaved CRMP has yet to be elucidated, as is the reason for nuclear translocation. Once the crystal structure of the cytoplasmic and nuclear-translocated forms of CRMPs is determined, a greater molecular understanding of why these forms can initiate neurodegeneration following CNS injury will be established. Such information will be particularly informative in the design of inhibitors of specific protein-protein interaction sites between cleaved CRMP and vital cytosolic or nuclear molecules.
AuthorsKasra Taghian, Jae Young Lee, Steven Petratos
JournalJournal of neurotrauma (J Neurotrauma) Vol. 29 Issue 9 Pg. 1728-35 (Jun 10 2012) ISSN: 1557-9042 [Electronic] United States
PMID22181040 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Semaphorin-3A
  • collapsin response mediator protein-1
  • collapsin response mediator protein-2
  • Calpain
Topics
  • Amino Acid Sequence
  • Animals
  • Brain Injuries (metabolism, pathology)
  • Calpain (metabolism)
  • Humans
  • Intercellular Signaling Peptides and Proteins (genetics, physiology)
  • Models, Molecular
  • Molecular Sequence Data
  • Nerve Degeneration (metabolism, pathology)
  • Nerve Tissue Proteins (genetics, physiology)
  • Phosphoproteins (genetics, physiology)
  • Phosphorylation
  • Protein Conformation
  • Semaphorin-3A (genetics, metabolism, physiology)
  • Spinal Cord Injuries (metabolism, pathology)
  • Translocation, Genetic (genetics)

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