Sclip, a Microtubule-destabilizing Factor, Interacts with Rasgrf1 and Inhibits Its Ability to Promote Rac Activation and Neurite Outgrowth.
From: Department of Biomolecular Sciences and Biotechnology, University of Milan, Italy. simona.baldassa@unimi.it
The Journal of biological chemistry
- Publish Date: Jan 2007
- ISSN: 0021-9258
- Volume: 282
- Issue: 4
- Pages: 2333-45
- Medium: Print
- Language: English
- Citation (JAMA): Baldassa Simona, Gnesutta Nerina, Fascio Umberto, et al. Sclip, a Microtubule-destabilizing Factor, Interacts with Rasgrf1 and Inhibits Its Ability to Promote Rac Activation and Neurite Outgrowth.. J. Biol. Chem. Jan 2007;282:2333-45
Abstract
RasGRF1 is a neuron-specific guanine nucleotide exchange factor for the small GTPases Ras and Rac. It is implicated in the regulation of memory formation and in the development of tolerance to drug abuse, although the mechanisms have been elucidated only in part. Here we report the isolation, by the yeast two-hybrid screen, of the microtubule-destabilizing factor SCLIP (SCG10-like protein) as a novel RasGRF1-interacting protein. This interaction requires the region spanning the Dbl-homology domain of RasGRF1, endowed with catalytic activity on Rac. In search for a possible function we found by biochemical means that SCLIP influences the signaling properties of RasGRF1, greatly reducing its ability to activate the Rac/p38 MAPK pathway, while the Ras/Erk one remains unaffected. Moreover, a potential role is suggested by transfection studies in neuronal PC12 cells in which RasGRF1 induces neurite outgrowth, and coexpression of SCLIP counteracts this effect, causing a dramatic decrease in the percentage of cells bearing neurites, which also appear significantly shortened. This study unveils a physical and functional interaction between RasGRF1 and SCLIP. We suggest that this novel interplay may have possible implications in mechanisms that regulate neuronal morphology and structural plasticity.
Mesh Headings (Keywords): Animals, Cells, Cultured, Enzyme Activation, Humans, Male, Mice, Mice, Inbred BALB C, Microtubule-Associated Proteins, Nerve Growth Factors, Neurites, Neuronal Plasticity, Neurons, Protein Binding, Proto-Oncogene Proteins c-akt, Rats, Rats, Sprague-Dawley, Signal Transduction, ras-GRF1
Check for Full Text / PubMed Unique Identifier (PMID): 17135267
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