RT Journal Article SR Electronic T1 TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6809 OP 6818 DO 10.1523/JNEUROSCI.5546-08.2009 VO 29 IS 21 A1 Heidi Stöhr A1 Julia B. Heisig A1 Peter M. Benz A1 Simon Schöberl A1 Vladimir M. Milenkovic A1 Olaf Strauss A1 Wendy M. Aartsen A1 Jan Wijnholds A1 Bernhard H. F. Weber A1 Heidi L. Schulz YR 2009 UL http://www.jneurosci.org/content/29/21/6809.abstract AB Photoreceptor ribbon synapses release glutamate in response to graded changes in membrane potential evoked by vast, logarithmically scalable light intensities. Neurotransmitter release is modulated by intracellular calcium levels. Large Ca2+-dependent chloride currents are important regulators of synaptic transmission from photoreceptors to second-order neurons; the molecular basis underlying these currents is unclear. We cloned human and mouse TMEM16B, a member of the TMEM16 family of transmembrane proteins, and show that it is abundantly present in the photoreceptor synaptic terminals in mouse retina. TMEM16B colocalizes with adaptor proteins PSD95, VELI3, and MPP4 at the ribbon synapses and contains a consensus PDZ class I binding motif capable of interacting with PDZ domains of PSD95. Furthermore, TMEM16B is lost from photoreceptor membranes of MPP4-deficient mice. This suggests that TMEM16B is a novel component of a presynaptic protein complex recruited to specialized plasma membrane domains of photoreceptors. TMEM16B confers Ca2+-dependent chloride currents when overexpressed in mammalian cells as measured by halide sensitive fluorescent protein assays and whole-cell patch-clamp recordings. The compartmentalized localization and the electrophysiological properties suggest TMEM16B to be a strong candidate for the long sought-after Ca2+-dependent chloride channel in the photoreceptor synapse.