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The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development.
- Source :
-
Developmental cell [Dev Cell] 2014 Feb 24; Vol. 28 (4), pp. 381-93. - Publication Year :
- 2014
-
Abstract
- Regulation of cargo transport via adaptor molecules is essential for neuronal development. However, the role of PDZ scaffolding proteins as adaptors in neuronal cargo trafficking is still poorly understood. Here, we show by genetic deletion in mice that the multi-PDZ domain scaffolding protein glutamate receptor interacting protein 1 (GRIP1) is required for dendrite development. We identify an interaction between GRIP1 and 14-3-3 proteins that is essential for the function of GRIP1 as an adaptor protein in dendritic cargo transport. Mechanistically, 14-3-3 binds to the kinesin-1 binding region in GRIP1 in a phospho-dependent manner and detaches GRIP1 from the kinesin-1 motor protein complex thereby regulating cargo transport. A single point mutation in the Thr956 of GRIP1 in transgenic mice impairs dendritic development. Together, our results show a regulatory role for GRIP1 during microtubule-based transport and suggest a crucial function for 14-3-3 proteins in controlling kinesin-1 motor attachment during neuronal development.<br /> (Copyright © 2014 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Carrier Proteins genetics
Carrier Proteins metabolism
Gene Knockout Techniques methods
Kinesins genetics
Mice
Mutation genetics
Nerve Tissue Proteins genetics
Protein Binding
Protein Transport genetics
Protein Transport physiology
Transcription Factors genetics
Transcription Factors metabolism
14-3-3 Proteins metabolism
Adaptor Proteins, Signal Transducing metabolism
Dendrites metabolism
Kinesins metabolism
Nerve Tissue Proteins metabolism
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1551
- Volume :
- 28
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Developmental cell
- Publication Type :
- Academic Journal
- Accession number :
- 24576423
- Full Text :
- https://doi.org/10.1016/j.devcel.2014.01.018