Cell-surface receptor-mediated control of postsynaptic organelle distribution in synaptic plasticity and experience-dependent dendritic spine maturation.

Synapses are diverse in their structural and functional properties and this diversity is important for brain function. A less appreciated aspect of synaptic diversity is at the level of organelle content. The spine apparatus (SA) is a postsynaptic organelle that is found in a subset of dendritic spines, with a key role in calcium signaling, spine maturation and plasticity. The mechanisms that determine why some spines contain a SA and others do not are largely unknown. Our preliminary findings indicate that the postsynaptic receptor GPR158 restricts the function of its novel interactor PLCXD2, a constitutively active phospholipase, and that this is required for SA incorporation and dendritic spine maturation during development. I hypothesize that GPR158-mediated control of PLCXD2 function regulates SA content in dendritic spines in synaptic plasticity and sensory experience-dependent circuit maturation.
Here, we will 1) uncover molecular mechanisms by which the GPR158-PLCXD2 complex regulates SA presence in spines; 2) establish the role of the GPR158-PLCXD2 complex in SA recruitment during homeostatic synaptic plasticity, and 3) assess the role of GPR158-PLCXD2-mediated SA recruitment in sensory experience-dependent spine maturation and dendritic calcium signaling in vivo. Together, this work will provide insight in the mechanisms regulating dendritic spine maturation, function and plasticity, processes that are perturbed in a range of brain disorders.