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

J.C. Geiger; Joanna Lipka; S. Hoyer; M.A. Schlager; Phebe Wulf; S. Weinges; J. Demmers; Casper Hoogenraad

doi:10.1016/j.devcel.2014.01.018

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

J.C. Geiger, Joanna Lipka, S. Hoyer, M.A. Schlager, Phebe Wulf, S. Weinges, J. Demmers, Casper Hoogenraad

Research output: Contribution to journal › Article › Academic › peer-review

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 language	English
Pages (from-to)	381-393
Number of pages	13
Journal	Developmental Cell
Volume	28
Issue number	4
DOIs	https://doi.org/10.1016/j.devcel.2014.01.018
Publication status	Published - 2014

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title = "The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development",

abstract = "Regulation of cargo transport via adaptor moleculesis essential for neuronal development. However,the role of PDZ scaffolding proteins asadaptors in neuronal cargo trafficking is still poorlyunderstood. Here, we show by genetic deletion inmice that the multi-PDZ domain scaffolding proteinglutamate receptor interacting protein 1 (GRIP1) isrequired for dendrite development. We identify aninteraction between GRIP1 and 14-3-3 proteinsthat is essential for the function of GRIP1 as anadaptor protein in dendritic cargo transport. Mechanistically,14-3-3 binds to the kinesin-1 bindingregion in GRIP1 in a phospho-dependent mannerand detaches GRIP1 from the kinesin-1 motor proteincomplex thereby regulating cargo transport. Asingle point mutation in the Thr956 of GRIP1 intransgenic mice impairs dendritic development.Together, our results show a regulatory role forGRIP1 during microtubule-based transport andsuggest a crucial function for 14-3-3 proteins incontrolling kinesin-1 motor attachment duringneuronal development.",

author = "J.C. Geiger and Joanna Lipka and S. Hoyer and M.A. Schlager and Phebe Wulf and S. Weinges and J. Demmers and Casper Hoogenraad",

year = "2014",

doi = "10.1016/j.devcel.2014.01.018",

language = "English",

volume = "28",

pages = "381--393",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "4",

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TY - JOUR

T1 - The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development

AU - Geiger, J.C.

AU - Lipka, Joanna

AU - Hoyer, S.

AU - Schlager, M.A.

AU - Wulf, Phebe

AU - Weinges, S.

AU - Demmers, J.

AU - Hoogenraad, Casper

PY - 2014

Y1 - 2014

N2 - Regulation of cargo transport via adaptor moleculesis essential for neuronal development. However,the role of PDZ scaffolding proteins asadaptors in neuronal cargo trafficking is still poorlyunderstood. Here, we show by genetic deletion inmice that the multi-PDZ domain scaffolding proteinglutamate receptor interacting protein 1 (GRIP1) isrequired for dendrite development. We identify aninteraction between GRIP1 and 14-3-3 proteinsthat is essential for the function of GRIP1 as anadaptor protein in dendritic cargo transport. Mechanistically,14-3-3 binds to the kinesin-1 bindingregion in GRIP1 in a phospho-dependent mannerand detaches GRIP1 from the kinesin-1 motor proteincomplex thereby regulating cargo transport. Asingle point mutation in the Thr956 of GRIP1 intransgenic mice impairs dendritic development.Together, our results show a regulatory role forGRIP1 during microtubule-based transport andsuggest a crucial function for 14-3-3 proteins incontrolling kinesin-1 motor attachment duringneuronal development.

AB - Regulation of cargo transport via adaptor moleculesis essential for neuronal development. However,the role of PDZ scaffolding proteins asadaptors in neuronal cargo trafficking is still poorlyunderstood. Here, we show by genetic deletion inmice that the multi-PDZ domain scaffolding proteinglutamate receptor interacting protein 1 (GRIP1) isrequired for dendrite development. We identify aninteraction between GRIP1 and 14-3-3 proteinsthat is essential for the function of GRIP1 as anadaptor protein in dendritic cargo transport. Mechanistically,14-3-3 binds to the kinesin-1 bindingregion in GRIP1 in a phospho-dependent mannerand detaches GRIP1 from the kinesin-1 motor proteincomplex thereby regulating cargo transport. Asingle point mutation in the Thr956 of GRIP1 intransgenic mice impairs dendritic development.Together, our results show a regulatory role forGRIP1 during microtubule-based transport andsuggest a crucial function for 14-3-3 proteins incontrolling kinesin-1 motor attachment duringneuronal development.

U2 - 10.1016/j.devcel.2014.01.018

DO - 10.1016/j.devcel.2014.01.018

M3 - Article

SN - 1534-5807

VL - 28

SP - 381

EP - 393

JO - Developmental Cell

JF - Developmental Cell

IS - 4

ER -

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

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