The Complexins (Cplxs) 1 and 2 are high affinity SNARE-interacting proteins. They regulate a late step in the synaptic vesicle fusion reaction with the plasma membrane, most likely by stabilizing the SNARE complex in order to maintain synaptic vesicles in a release competent state. Different from the Cplxs 1 and 2 are the Cplxs 3 and 4. They show limited homology to the Cplxs 1 and 2, possess a C-terminal CAAX-box motif for membrane interaction and are predominantly expressed at ribbon synapses of the vertebrate retina. From a previous study examining Cplx 3/4 double-knockout mice, we know that the Cplxs 3 and 4 have diverse functions in neurotransmitter release from photoreceptor ribbon synapses: they suppress tonic and facilitate evoked release, and they play a putative role in the adaptation-dependent regulation of the availability of ribbon-tethered releasable synaptic vesicles. However, the most fundamental question in the field has not been approached so far: what are the underlying molecular and cell biological mechanisms of retinal Cplx function? To address this question, we will study the adaptation-dependent expression (RNA, protein) of the Cplxs 3 and 4, and their switching between soluble and insoluble (membrane-associated) forms, which may depend on farnesylation of their unique C terminus. Moreover, we will search for interaction partners, which may influence the cell biology of the Cplxs 3 and 4 in general and their functional availability in particular (regulators), and which may modulate downstream Cplx functions and thereby transmitter release in an activity-dependent manner (effectors).
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