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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Schreiner, Dietmar Keeler, Austin B. Weiner, Joshua A. |
| Description | Author Affiliation: Keeler AB ( From the Department of Biology and Neuroscience Graduate Program, The University of Iowa, Iowa City, Iowa 52242.); Schreiner D ( From the Department of Biology and.); Weiner JA ( From the Department of Biology and Neuroscience Graduate Program, The University of Iowa, Iowa City, Iowa 52242 joshua-weiner@uiowa.edu.) |
| Abstract | The γ-protocadherins (γ-Pcdhs) are a family of 22 adhesion molecules with multiple critical developmental functions, including the proper formation of dendritic arbors by forebrain neurons. The γ-Pcdhs bind to and inhibit focal adhesion kinase (FAK) via a constant C-terminal cytoplasmic domain shared by all 22 proteins. In cortical neurons lacking the γ-Pcdhs, aberrantly high activity of FAK and of PKC disrupts dendrite arborization. Little is known, however, about how γ-Pcdh function is regulated by other factors. Here we show that PKC phosphorylates a serine residue situated within a phospholipid binding motif at the shared γ-Pcdh C terminus. Western blots using a novel phospho-specific antibody against this site suggest that a portion of γ-Pcdh proteins is phosphorylated in the cortex in vivo. We find that PKC phosphorylation disrupts both phospholipid binding and the γ-Pcdh inhibition of (but not binding to) FAK. Introduction of a non-phosphorylatable (S922A) γ-Pcdh construct into wild-type cortical neurons significantly increases dendrite arborization. This same S922A construct can also rescue dendrite arborization defects in γ-Pcdh null neurons cell autonomously. Consistent with these data, introduction of a phosphomimetic (S/D) γ-Pcdh construct or treatment with a PKC activator reduces dendrite arborization in wild-type cortical neurons. Together, these data identify a novel mechanism through which γ-Pcdh control of a signaling pathway important for dendrite arborization is regulated. |
| ISSN | 00219258 |
| e-ISSN | 1083351X |
| Journal | Journal of Biological Chemistry |
| Issue Number | 34 |
| Volume Number | 290 |
| Language | English |
| Publisher | American Society for Biochemistry and Molecular Biology (United States) |
| Publisher Date | 2015-08-21 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cadherins Metabolism Cerebral Cortex Dendrites Focal Adhesion Kinase 1 Neurogenesis Genetics Protein Kinase C Amino Acid Sequence Animals Drug Effects Growth & Development Ultrastructure Embryo, Mammalian Antagonists & Inhibitors Gene Expression Regulation, Developmental Intracellular Signaling Peptides And Proteins Membrane Proteins Mice Mice, Inbred C57BL Molecular Sequence Data Phosphatidylinositols Phosphorylation Primary Cell Culture Protein Binding Protein Structure, Tertiary Signal Transduction Tetradecanoylphorbol Acetate Pharmacology Research Support, N.I.H., Extramural Biochemistry Molecular Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology |
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