Project Details
Projekt
Analyzing the Complexins of the photoreceptor ribbon synapses in mouse retina
Subject Area
Molecular Biology and Physiology of Neurons and Glial Cells
Term
from 2019 to 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 428863786
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).
DFG Programme
Research Grants
