TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals

Stoehr, Heidi and Heisig, Julia B. and Benz, Peter M. and Schoeberl, Simon and Milenkovic, Vladimir M. and Strauss, Olaf and Aartsen, Wendy M. and Wijnholds, Jan and Weber, Bernhard H. F. and Schulz, Heidi L. (2009) TMEM16B, A Novel Protein with Calcium-Dependent Chloride Channel Activity, Associates with a Presynaptic Protein Complex in Photoreceptor Terminals. JOURNAL OF NEUROSCIENCE, 29 (21). pp. 6809-6818. ISSN 0270-6474,

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Abstract

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.

Item Type: Article
Uncontrolled Keywords: ROD PHOTORECEPTORS; TRANSMITTER RELEASE; SALAMANDER RETINA; MAMMALIAN RETINA; INNER SEGMENTS; MEMBRANE; EXPRESSION; MPP4; LOCALIZATION; HOMEOSTASIS;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Augenheilkunde
Medicine > Lehrstuhl für Humangenetik
Depositing User: Dr. Gernot Deinzer
Date Deposited: 15 Sep 2020 10:57
Last Modified: 15 Sep 2020 10:57
URI: https://pred.uni-regensburg.de/id/eprint/28958

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