RGD Reference Report - Rab13 regulates neurite outgrowth in PC12 cells through its effector protein, JRAB/MICAL-L2. - Rat Genome Database

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Rab13 regulates neurite outgrowth in PC12 cells through its effector protein, JRAB/MICAL-L2.

Authors: Sakane, A  Honda, K  Sasaki, T 
Citation: Sakane A, etal., Mol Cell Biol. 2010 Feb;30(4):1077-87. doi: 10.1128/MCB.01067-09. Epub 2009 Dec 14.
RGD ID: 8553724
Pubmed: PMID:20008558   (View Abstract at PubMed)
PMCID: PMC2815571   (View Article at PubMed Central)
DOI: DOI:10.1128/MCB.01067-09   (Journal Full-text)

Neurite outgrowth is the first step in the processes of neuronal differentiation and regeneration and leads to synaptic polarization and plasticity. Rab13 small G protein shows an increased mRNA expression level during neuronal regeneration; it is therefore thought to be involved in this process. We previously identified JRAB (junctional Rab13-binding protein)/MICAL-L2 (molecules interacting with CasL-like 2) as a novel Rab13 effector protein. Here, we show that Rab13 regulates neurite outgrowth in the rat pheochromocytoma cell line PC12 through an interaction with JRAB/MICAL-L2. The expression of JRAB/MICAL-L2 alone inhibits neurite outgrowth, whereas coexpression of the dominant active form of Rab13 rescues this effect. We also demonstrate an intramolecular interaction between the N-terminal calponin-homology (CH) and LIM domains of JRAB/MICAL-L2 and the C-terminal coiled-coil domain. Finally, we show that the binding of Rab13 to JRAB/MICAL-L2 stimulates the interaction of JRAB/MICAL-L2 with actinin-4, an actin-binding protein, which localizes to the cell body and the tips of the neurites in PC12 cells. These results suggest that Rab13 and JRAB/MICAL-L2 may act to transfer actinin-4 from the cell body to the tips of neurites, where actinin-4 is involved in the reorganization of the actin cytoskeleton which results in neurite outgrowth.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
actin filament polymerization involved_inIMP 8553724PMID:20008558UniProt 
neuron projection development involved_inIMP 8553724; 8553724PMID:20008558UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neuron projection located_inIDA 8553724; 8553724PMID:20008558UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Actn4  (actinin alpha 4)
Micall2  (MICAL-like 2)
Rab13  (RAB13, member RAS oncogene family)


Additional Information