Title

The ubiquitin ligase Rnf6 regulates local LIM kinase 1 levels in axonal growth cones

UMMS Affiliation

Programs in Gene Function and Expression; Program in Molecular Medicine

Date

10-6-2005

Document Type

Article

Medical Subject Headings

Actins; Animals; CHO Cells; COS Cells; Cercopithecus aethiops; Cricetinae; Cricetulus; DNA-Binding Proteins; Gene Expression Regulation, Developmental; Growth Cones; Hippocampus; Humans; Lim Kinases; Mice; Proteasome Endopeptidase Complex; Protein Kinases; RNA Interference; RNA, Small Interfering; Ubiquitin

Disciplines

Genetics and Genomics

Abstract

LIM kinase 1 (LIMK1) controls important cellular functions such as morphogenesis, cell motility, tumor cell metastasis, development of neuronal projections, and growth cone actin dynamics. We have investigated the role of the RING finger protein Rnf6 during neuronal development and detected high Rnf6 protein levels in developing axonal projections of motor and DRG neurons during mouse embryogenesis as well as cultured hippocampal neurons. RNAi-mediated knock-down experiments in primary hippocampal neurons identified Rnf6 as a regulator of axon outgrowth. Consistent with a role in axonal growth, we found that Rnf6 binds to, polyubiquitinates, and targets LIMK1 for proteasomal degradation in growth cones of primary hippocampal neurons. Rnf6 is functionally linked to LIMK1 during the development of axons, as the changes in axon outgrowth induced by up- or down-regulation of Rnf6 levels can be restored by modulation of LIMK1 expression. Thus, these results assign a specific role for Rnf6 in the control of cellular LIMK1 concentrations and indicate a new function for the ubiquitin/proteasome system in regulating local growth cone actin dynamics.

Rights and Permissions

Citation: Genes Dev. 2005 Oct 1;19(19):2307-19. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

16204183