Neurons use multiple modes of endocytosis, including clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE), during mild and intense neuronal activity, respectively, to maintain stable neurotransmission. While molecular players modulating CME are well characterized, factors regulating ADBE and mechanisms coordinating CME and ADBE activations remain poorly understood. Here we report that Minibrain/DYRK1A (Mnb), a kinase mutated in autism and up-regulated in Down’s syndrome, plays a novel role in suppressing ADBE. We demonstrate that Mnb, together with calcineurin, delicately coordinates CME and ADBE by controlling the phosphoinositol phosphatase activity of synaptojanin (Synj) during varying synaptic demands. Functional domain analyses reveal that Synj’s 5′-phosphoinositol phosphatase activity suppresses ADBE, while SAC1 activity is required for efficient ADBE. Consequently, Parkinson’s disease mutation in Synj’s SAC1 domain impairs ADBE. These data identify Mnb and Synj as novel regulators of ADBE and further indicate that CME and ADBE are differentially governed by Synj’s dual phosphatase domains.
Minibrain kinase and calcineurin coordinate activity-dependent bulk endocytosis through synaptojanin
J. Geng’s present address is School of Life Science and Technology, Southeast University, Nanjing, Jiangsu, China.
- Award Id(s): R01NS080946,R01NS102260
- Views Icon Views
- Share Icon Share
- Search Site
Yi-Jheng Peng, Junhua Geng, Ying Wu, Cristian Pinales, Jennifer Langen, Yen-Ching Chang, Christopher Buser, Karen T. Chang; Minibrain kinase and calcineurin coordinate activity-dependent bulk endocytosis through synaptojanin. J Cell Biol 6 December 2021; 220 (12): e202011028. doi: https://doi.org/10.1083/jcb.202011028
Download citation file: