The GRIP1/14-3-3 Pathway Coordinates Cargo Trafficking and Dendrite Development

JC Geiger, J Lipka, I Segura, S Hoyer, Max Schlager, PS Wulf, S Weinges, Jeroen Demmers, CC Hoogenraad, A Acker-Palmer

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Scopus)

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.
Original languageUndefined/Unknown
Pages (from-to)381-393
Number of pages13
JournalDevelopmental Cell
Volume28
Issue number4
DOIs
Publication statusPublished - 2014

Research programs

  • EMC MGC-02-21-01
  • EMC ONWAR-01-94-01

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