Neuronal Morphogenesis is Regulated by the Interplay Between Cyclin-dependent Kinase 5 and the Ubiquitin Ligase Mind Bomb 1.
From: Department of Human Genetics, Center for Neurodegenerative Diseases, School of Medicine, Emory University, Atlanta, Georgia 30322, USA.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Aug 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 35
- Pages: 9503-12
- Medium: Internet
- Language: English
- Citation (JAMA): Choe Eun-Ah, Liao Lujian, Zhou Jian-Ying, et al. Neuronal Morphogenesis is Regulated by the Interplay Between Cyclin-dependent Kinase 5 and the Ubiquitin Ligase Mind Bomb 1.. J. Neurosci. Aug 2007;27:9503-12
Abstract
Neuronal communication requires the coordinated assembly of polarized structures including axons, dendrites, and synapses. Here, we report the identification of a ubiquitin ligase mind bomb 1 (Mib1) in the postsynaptic density and the characterization of its role in neuronal morphogenesis. Expression of Mib1 inhibits neurite outgrowth in cell culture and its gene deletion enhances synaptic growth at the neuromuscular junction in Drosophila. The analysis of Mib1 interactome by mass spectrometry revealed that Mib1 primarily interacts with membrane trafficking proteins [e.g., EEA1 (early endosomal antigen 1), Rab11-interacting proteins, and SNAP25 (synaptosomal-associated protein of 25 kDa)-like protein] and cell adhesion components (e.g., catenin, coronin, dystrobrevin, and syndecan), consistent with its previously reported function in protein sorting. More interestingly, Mib1 is associated with deubiquitinating enzymes, BRCC36 and the mammalian ortholog of fat facets, and a number of kinases, such as casein kinase II, MARK (microtubule affinity regulating kinase)/PAR1, and cyclin-dependent kinase 5 (CDK5). Further characterization of the Mib1-CDK5 interaction indicated that the N-terminal domain of Mib1 directly binds to the regulatory subunit p35 of the CDK5 complex. In cell culture, Mib1 induces the relocalization of p35/CDK5 without affecting its degradation. Surprisingly, p35/CDK5 downregulates the protein level of Mib1 by its kinase activity, and completely rescues the Mib1-induced inhibitory effect on neurite morphology. p35/CDK5 also genetically interacts with Mib1 in the fly according to the rough-eye phenotype. The data strongly support that the negative interplay between Mib1 and p35/CDK5 may integrate the activities of multiple pathways during neuronal development.
Mesh Headings (Keywords): Animals, Brain, Cells, Cultured, Cercopithecus aethiops, Cyclin-Dependent Kinase 5, Drosophila melanogaster, Embryo, Mammalian, Embryo, Nonmammalian, Gene Expression Regulation, Humans, Immunoprecipitation, Mass Spectrometry, Neurites, Neurons, Rats, Rats, Sprague-Dawley, Transfection, Ubiquitin-Protein Ligases
Check for Full Text / PubMed Unique Identifier (PMID): 17728463
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.