Journal article
Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking
Proceedings of the National Academy of Sciences - PNAS, v 109(11), pp 4116-4121
13 Mar 2012
PMID: 22371566
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Synaptic transmission is mediated by a complex set of molecular events that must be coordinated in time and space. While many proteins that function at the synapse have been identified, the signaling pathways regulating these molecules are poorly understood. Pak5 (p21-activated kinase 5) is a brain-specific isoform of the group II Pak kinases whose substrates and roles within the central nervous system are largely unknown. To gain insight into the physiological roles of Pak5, we engineered a Pak5 mutant to selectively radiolabel its substrates in murine brain extract. Using this approach, we identified two novel Pak5 substrates, Pacsin1 and Synaptojanin1, proteins that directly interact with one another to regulate synaptic vesicle endocytosis and recycling. Pacsin1 and Synaptojanin1 were phosphorylated by Pak5 and the other group II Paks in vitro, and Pak5 phosphorylation promoted Pacsin1-Synaptojanin1 binding both in vitro and in vivo. These results implicate Pak5 in Pacsin1- and Synaptojanin1-mediated synaptic vesicle trafficking and may partially account for the cognitive and behavioral deficits observed in group II Pak-deficient mice.
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Details
- Title
- Identification of neuronal substrates implicates Pak5 in synaptic vesicle trafficking
- Creators
- Todd I. Strochlic - Fox Chase Cancer CenterSusanna Concilio - Fox Chase Cancer CenterJulien Viaud - InsermRyan A. Eberwine - Fox Chase Cancer CenterLisa Epstein Wong - Rutgers, The State University of New JerseyAudrey Minden - Rutgers, The State University of New JerseyBenjamin E. Turk - Yale UniversityMarkus Plomann - University of CologneJeffrey R. Peterson - Fox Chase Cancer Center
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, v 109(11), pp 4116-4121
- Publisher
- Natl Acad Sciences
- Number of pages
- 6
- Grant note
- W. W. Smith Charitable Trust P30CA006927 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) R01 GM083025; T32 CA009035; P30 CA006927 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01GM083025 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) PF-11-068-01-TBE / American Cancer Society
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000301426700025
- Scopus ID
- 2-s2.0-84858248556
- Other Identifier
- 991020837746004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cell Biology