RGD Reference Report - Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms. - Rat Genome Database

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Kalirin Dbl-homology guanine nucleotide exchange factor 1 domain initiates new axon outgrowths via RhoG-mediated mechanisms.

Authors: May, V  Schiller, MR  Eipper, BA  Mains, RE 
Citation: May V, etal., J Neurosci 2002 Aug 15;22(16):6980-90.
RGD ID: 628431
Pubmed: PMID:12177196   (View Abstract at PubMed)
PMCID: PMC6757900   (View Article at PubMed Central)
DOI: DOI:20026718   (Journal Full-text)

The large multidomain Kalirin and Trio proteins containing dual Rho GTPase guanine nucleotide exchange factor (GEF) domains have been implicated in the regulation of neuronal fiber extension and pathfinding during development. In mammals, Kalirin is expressed predominantly in the nervous system, whereas Trio, broadly expressed throughout the body, is expressed at a lower level in the nervous system. To evaluate the role of Kalirin in fiber initiation and outgrowth, we microinjected cultured sympathetic neurons with vectors encoding Kalirin or with Kalirin antisense oligonucleotides, and we assessed neuronal fiber growth in a serum-free, satellite cell-free environment. Kalirin antisense oligonucleotides blocked the continued extension of preexisting axons. Kalirin overexpression induced the prolific sprouting of new axonal fibers that grew at the normal rate; the activity of Kalirin was entirely dependent on the activity of the first GEF domain. KalGEF1-induced sprouting of new fibers from lamellipodial structures was accompanied by extensive actin cytoskeleton reorganization. The kalGEF1 phenotype was mimicked by constitutively active RhoG and was blocked by RhoG inhibitors. Constitutively active Rac1, RhoA, and Cdc42 were unable to initiate new axons, whereas dominant-negative Rac1, RhoA, and Cdc42 failed to block axon sprouting. Thus Kalirin, acting via RhoG in a novel manner, plays a central role in establishing the morphological phenotypic diversity that is essential to the connectivity of the developing nervous system.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KalrnRataxonogenesis  IDA  RGD 
KalrnRatintracellular signal transduction involved_inIDA PMID:12177196HGNC-UCL 
KalrnRatintracellular signal transduction  IDA  RGD 
KalrnRatnervous system development involved_inIDA PMID:12177196HGNC-UCL 
KalrnRatnervous system development  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
KalrnRatguanyl-nucleotide exchange factor activity enablesTAS PMID:12177196HGNC-UCL 
KalrnRatguanyl-nucleotide exchange factor activity  TAS  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Kalrn  (kalirin, RhoGEF kinase)


Additional Information