The TRIM9/TRIM67 neuronal interactome reveals novel activators of morphogenesis
| Autor: | Tsungyo Ho, Andrew J. Bock, Erica W. Cloer, Joel Anil, Dennis Goldfarb, Stephanie L. Gupton, Christopher Hardie, M. Ben Major, Nicholas P. Boyer, Shalini Menon, Emma C. Johnson |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Ubiquitin-Protein Ligases Growth Cones Morphogenesis Nerve Tissue Proteins Computational biology Biology Interactome Hippocampus Exocytosis Tripartite Motif Proteins Ubiquitin Protein Interaction Mapping Animals Protein Interaction Maps Pseudopodia Cytoskeleton Molecular Biology KIF1A Adaptor Proteins Signal Transducing Mice Knockout Neurons Colocalization Neuronal Growth Cell Biology Articles Axons Cell biology Mice Inbred C57BL Cytoskeletal Proteins nervous system Biotinylation biology.protein Axon guidance Female Filopodia |
| Zdroj: | Molecular Biology of the Cell |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | TRIM9 and TRIM67 are neuronally-enriched E3 ubiquitin ligases essential for appropriate morphogenesis of cortical and hippocampal neurons and fidelitous responses to the axon guidance cue netrin-1. Deletion of murine Trim9 or Trim67 results in neuroanatomical defects and striking behavioral deficits, particularly in spatial learning and memory. TRIM9 and TRIM67 interact with cytoskeletal and exocytic proteins, but the full interactome is not known. Here we performed the unbiased proximity-dependent biotin identification (BioID) approach to define TRIM9 and TRIM67 protein-protein proximity network in developing cortical neurons and identified neuronal putative TRIM interaction partners. Candidates included cytoskeletal regulators, cytosolic protein transporters, exocytosis and endocytosis regulators, and proteins necessary for synaptic regulation. A subset of high priority candidates was validated, including Myo16, Coro1A, SNAP47, ExoC1, GRIP1, PRG-1, and KIF1A. For a subset of validated candidates, we utilized TIRF microscopy to demonstrate dynamic colocalization with TRIM proteins at the axonal periphery, including at the tips of filopodia. Further analysis demonstrated the RNAi-based knockdown of the unconventional myosin Myo16 in cortical neurons altered axonal branching patterns in a TRIM9 and netrin-1 dependent manner. Future analysis of other validated candidates will likely identify novel proteins and mechanisms by which TRIM9 and TRIM67 regulate neuronal form and function. |
| Databáze: | OpenAIRE |
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