selective interaction of syntaxin 1a with kcnq2 possible implications for specific modulation of presynaptic activity1突触融合蛋白的选择性相互作用与kcnq2可能影响突触前活动的特定的调制.pdfVIP

Selective Interaction of Syntaxin 1A with KCNQ2: Possible Implications for Specific Modulation of Presynaptic Activity 1 1 2 1 1 3 Noa Regev , Nurit Degani-Katzav , Alon Korngreen , Adi Etzioni , Sivan Siloni , Alessandro Alaimo , 1 3 1 1 Dodo Chikvashvili , Alvaro Villarroel , Bernard Attali , Ilana Lotan * 1 Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat-Aviv, Israel, 2 Mina Everard Goodman Faculty of life Sciences, ´ ´ Bar-Ilan University, Ramat-Gan, Israel, 3 Unidad de Biofısica, CSIC-Universidad del Paıs Vasco (UPV)/Euskal Herriko Unibersitatea, UPV, Leioa, Spain Abstract KCNQ2/KCNQ3 channels are the molecular correlates of the neuronal M-channels, which play a major role in the control of neuronal excitability. Notably, they differ from homomeric KCNQ2 channels in their distribution pattern within neurons, with unique expression of KCNQ2 in axons and nerve terminals. Here, combined reciprocal coimmunoprecipitation and two- electrode voltage clamp analyses in Xenopus oocytes revealed a strong association of syntaxin 1A, a major component of the exocytotic SNARE complex, with KCNQ2 homomeric channels resulting in a ,2-fold reduction in macroscopic conductance and ,2-fold slower activation kinetics. Remarkably, the interaction of KCNQ2/Q3 heteromeric channels with syntaxin 1A was significantly weaker and KCNQ3 homomeric channels were practically resistant to syntaxin 1A. Analysis of different KCNQ2 and KCNQ3 chimeras and deletion mutants combined with in-vitro