Rab13 regulates neurite outgrowth in PC12 cells through its effector protein, JRAB/MICAL-L2.
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.
Sakane
Ayuko
A
Department of Biochemistry, Institute of Health Biosciences, University of Tokushima Graduate School, 3-18-15 Kuramato-cho, Tokushima 770-8503, Japan.
Honda
Kazufumi
K
Sasaki
Takuya
T
D000199:Actins / Q000378:metabolism; D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins; D016501:Neurites / Q000378:metabolism*; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats
D000199:Actins; D003598:Cytoskeletal Proteins; C512298:JRAB protein, mouse; D008840:Microfilament Proteins; D020558:GTP Phosphohydrolases; C541433:Rab13 protein, rat