The M domain in UNC-13 regulates the probability of neurotransmitter release
Haowen Liu,
Lei Li,
Seema Sheoran,
Yi Yu,
Janet E. Richmond,
Jingyao Xia,
Jing Tang,
Jie Liu,
Zhitao Hu
Affiliations
Haowen Liu
Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research (CJCADR), The University of Queensland, Brisbane, QLD 4072, Australia
Lei Li
Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research (CJCADR), The University of Queensland, Brisbane, QLD 4072, Australia
Seema Sheoran
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
Yi Yu
Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research (CJCADR), The University of Queensland, Brisbane, QLD 4072, Australia
Janet E. Richmond
Department of Biological Sciences, University of Illinois at Chicago, Chicago, IL 60607, USA
Jingyao Xia
Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research (CJCADR), The University of Queensland, Brisbane, QLD 4072, Australia
Jing Tang
Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research (CJCADR), The University of Queensland, Brisbane, QLD 4072, Australia
Jie Liu
Neuroscience Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, VIC 3800, Australia
Zhitao Hu
Queensland Brain Institute, Clem Jones Centre for Ageing Dementia Research (CJCADR), The University of Queensland, Brisbane, QLD 4072, Australia; Corresponding author
Summary: Synapses exhibit multiple forms of short-term plasticities, which have been attributed to the heterogeneity of neurotransmitter release probability. However, the molecular mechanisms that underlie the differential release states remain to be fully elucidated. The Unc-13 proteins appear to have key roles in synaptic function through multiple regulatory domains. Here, we report that deleting the M domain in Caenorhabditis elegans UNC-13MR leads to a significant increase in release probability, revealing an inhibitory function of this domain. The inhibitory effect of this domain is eliminated when the C1 and C2B domains are absent or activated, suggesting that the M domain inhibits release probability by suppressing the activity of C1 and C2B domains. When fused directly to the MUNC2C fragment of UNC-13, the M domain greatly enhances release probability. Thus, our findings reveal a mechanism by which the UNC-13 M domain regulates synaptic transmission and provides molecular insights into the regulation of release probability.
