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New piece in the puzzle of neuronal communication

February 2014. Detailed knowledge of the mechanisms that underlie neuronal communication is essential to better understand brain function and pathological conditions. Neurons can modulate their signal input not only by altering the area covered by their dendritic trees, but also by adapting the strength of their synapses. 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. A team of scientists led by Amparo Acker-Palmer has shown by genetic deletion in mice that the multi-PDZ domain scaffolding protein glutamate receptor interacting protein 1 (GRIP1) is required for dendrite development. The Frankfurt scientists identified 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, their 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. These findings provide molecular targets to investigate the cargo transport machinery in neurological and neurodevelopmental disease models.
Amparo Acker-Palmer
Institute for Cell Biology and Neuroscience
Buchmann Institute for Molecular Life Sciences
Goethe University Frankfurt
Max von Laue Str. 15
60438  Frankfurt am Main, Germany
e-mail: Acker-Palmer@bio.uni-frankfurt.de
Full reference: Geiger JC, Lipka J, Segura I, Hoyer S, Schlager MA, Wulf PS, Weinges S, Demmers J, Hoogenraad CC, Acker-Palmer A (2014) The GRIP1/14-3-3 pathway coordinates cargo trafficking and dendrite development. Dev Cell 28:381-393 [Link to paper]