GRASP-1 regulates endocytic receptor recycling and synaptic plasticity.

Remodeling of synapses is a fundamental mechanism for information storage and processing in the brain. Previous studies showed that the endosomal pathway plays a central role in synapse formation and plasticity. A popular model holds that recycling endosomes in dendrites provide the local intracellular pool of postsynaptic receptors for long-term potentiation (LTP), a widely studied cellular model for learning and memory formation. However, we are far from a complete understanding how endocytic receptor sorting and recycling is organized and coordinated in dendrites. Especially, the molecular mechanisms that couple specific endosomal trafficking routes during LTP are poorly understood. In a recent paper we discovered that the coiled-coil protein GRIP-associated protein-1 (GRASP-1) is a neuron-specific effector of the small GTPase Rab4 and key component of AMPA receptor recycling machinery in dendrites.1 GRASP-1 is essential for maintenance of spine morphology and important for LTP. GRASP-1 connects Rab4 and Rab11 recycling endosomal domains through the interaction with target (t)-SNARE syntaxin 13, which constitutes a new principle for regulating endosomal recycling. Here, we summarize our recently reported observations and further discuss their possible implications.