Wikipedia Proposal: Collapsin Response Mediator Protein Family. '
Presented by: Paul Lavadera, Grace Kwak, and Brian Ford.
General Description
editCollapsin Reponse Mediator Proteins (CRMPs) consist of five cytosolic phosphoproteins, CRMP1-5. CRMP family is also known as Unc-33-like proteins (Ulip), dihydropyrimidinase-related proteins (DRP), TUC (TOAD/Ulip/DRP), and dihydropyrimidinase-like proteins. They are strongly expressed throughout the development of nervous system.
History
editAmong the five members of the family, CRMP2 was first identified in 1995 by Goshima and his colleagues. CRMP2 was identified as an intracellular messenger in the transduction of the extracellular semaphoring 3A (Sema3A) signal, which induces the growth cone-collapse in chieck dorsal root ganglia. CRMP2 is the most well-studied CRMP of its family. Only CRMP2 is expressed in large amounts in adult neurons and oligodendrocytes, while CRMP1 and CRMP3-5 are expressed in small amounts in specific parts of the olfactory love, hippocampus, or cerebellum and in certain areas of oligodendrocytes. In this section, we will develop further discovery of the CRMP family.
Main Points
editImportant Functions in Cell
edit- Neuronal migration
- By phenotypic analysis of CRMP-deficient mice during cortical development, retardation in radial migration is observed and these suggest that CRMP1 is involved in regulating neuronal migration.
- Neuronal network formation and synapse formation
- Phosphorylation of CRMP1 and CRMP2 are essential for Sema3A-regulated axonal guidance.
- CRMP2 directly binds to cytoplasmic loops of presynaptic N-type voltage-gated Ca2+ channels (Cav2.2) and its interaction results in increase in Cav2.2 current density, increase in Ca2+ influx into nerve terminals and its synaptic strength.
- Maintenance of neuronal circuit and synaptic plasticity
- CRMPs may play a role in the regulation of the neuron regeneration and in synaptic plasticity. In the adult, CRMPs are expressed especially in areas that are involved in neurogenesis and/or plasticity.
Regulation of CRMP expression
edit- CRMPs’ expression is regulated during the development of the nervous system. In general, they are highly expressed in post-mitotic neural cells from early embryonic life. Their expression is maximized in the first postnatal week and is significantly downregulated in adult nervous system.
- Further description the expression of each CRMP and difference in their regulation in the developing and adult nervous system.
Activation of CRMP
edit- Injury-induced, pro-apoptotic, calcium-dependent proteases act as key initiator of CRMP cleavage
- Cleavage product is a C-terminus truncated 55 to 58 kDa form of CRMP and interacts with vital cytosolic or nuclear molecules
- Structure of cleaved form of CRMP yet to be determined, making it difficult to understand the protein-protein interactions and why these forms can initiate neurodegeneration after CNS injury
Clinical significance
edit- The expression of CRMPs is altered in neurodegenerative diseases and these proteins may play an essential role in the pathogenesis of disorders in the nervous system, including Alzheimer’s disease, Parkinson’s disease, schizophrenia, …etc.
List of CRMPs (and Associated disorders)
edit| CRMP | Phenotype in knockout | Function |
|---|---|---|
| CRMP1 | Information | Information |
| CRMP2 | Information | Information |
| CRMP3 | Information | Information |
| CRMP4 | Information | Information |
| CRMP5 | Information | Information |
Current Research Topics
editReferences
edit1. Charrier E., Reibel S., Rogemond V., Aguera M., Thomasset N., and Honnorat J. (2003) Collapsin response mediator proteins (CRMPs): involvement in nervous system development and adult neurodegenerative disorders. Molecular Neurobiology, 28(1), 51-63.
2. Wang Y., Brittain J.M., Wilson S.M., and Khanna R. (2010) Emerging roles of collapsin response mediator proteins (CRMPs) as regulators of voltage-gated calcium channels and synaptic transmission. Communicative & Integrative Biology, 3(2), 172-175.
3. Yamashita N., and Goshima Y. (2012) Collapsin response mediator proteins regulate neuronal development and plasticity by switching their phosphorylation status. Molecular Neurobiology, 45(2), 234-246.
4. Hou ST, Jiang SX, Smith RA. (2008) Permissive and repulsive cues and signalling pathways of axonal outgrowth and regeneration. International review of cell and molecular biology, 267:125-81.
5. Hensley K, Venkova K, Christov A, Gunning W, Park J. (2011) Collapsin response mediator protein-2: an emerging pathologic feature and therapeutic target for neurodisease indications. Molecular Neurobiology, 43(3):180-91.
6. Soutar MP, Thornhill P, Cole AR, Sutherland C. (2009) Increased CRMP2 phosphorylation is observed in Alzheimer's disease; does this tell us anything about disease development? Current Alzheimer research, 6(3):269-78.
7. Taghian K., Lee, JY., Petratos, S. (2012) Phosphorylation and Cleavage of the Family of Collapsin Response Mediator Proteins May Play a Central Role in Neurodegeneration after CNS Trauma: Journal of Neurotrauma, 29(9):1728-1735.
Division of workload:
editWe have agreed to schedule group sessions where we can work together on the various parts of this project. This will result in a cohesive article that best explains our topic.