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Publication : The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development.

First Author  Geiger JC Year  2014
Journal  Dev Cell Volume  28
Issue  4 Pages  381-93
PubMed ID  24576423 Mgi Jnum  J:244676
Mgi Id  MGI:5913455 Doi  10.1016/j.devcel.2014.01.018
Citation  Geiger JC, et al. (2014) The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development. Dev Cell 28(4):381-93
abstractText  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.
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