Phosphorylation of Collapsin Response Mediator Protein 1 (CRMP1) at Tyrosine 504 residue regulates Semaphorin 3A ‐induced cortical dendritic growth

AbstractCollapsin Response Mediator Proteins (CRMPs) have been identified as mediating proteins of repulsive axon guidance cue Semaphorin ‐3A (Sema3A). Phosphorylation of CRMPs plays a crucial role in the Sema3A signaling cascade. It has been shown that Fyn phosphorylates CRMP1 at Tyrosine 504 residue (Tyr504); however, the physiological role of this phosphorylation has not been examined. We found that CRMP1 was the most strongly ph osphorylated by Fyn among the five members of CRMPs. We confirmed Tyr504 phosphorylation of CRMP1 by Fyn. Immunocytochemistry of mouse dorsal root ganglion (DRG) neurons showed that phosphotyrosine signal in the growth cones was transiently increased in the growth cones upon Sema3A stimulation. Tyr5 04‐phosphorylated CRMP1 also tended to increase after Sema3A simulation. Ectopic expression of a single amino acid mutant of CRMP1 replacing Tyr504 with Phenylalanine (CRMP1‐Tyr504Phe) suppressed Sema3A‐induced growth cone collapse response in chick DRG neurons. CRMP1‐Tyr504Phe expression in mouse hippocampal neurons also suppressed Sema3A‐ but not Sema3F‐induced growth cone collapse response. Immunohistochemistry showed that Tyr504‐phosphorylated CRMP1 was present in the cell bodies and in the dendritic processes of mouse cortical neurons. CRMP1‐Tyr504Phe suppressed Sema3A‐i nduced dendritic growth of primary cultured mouse cortical neurons as well as the dendritic development of cortical pyramidal neuronsin vivo.Fyn+/ ‐;Crmp1+/ ...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research