Minibrain kinase and calcineurin coordinate activity-dependent bulk endocytosis through synaptojanin

DYRK1A
DOI: 10.1083/jcb.202011028 Publication Date: 2021-10-01T17:17:09Z
ABSTRACT
Neurons use multiple modes of endocytosis, including clathrin-mediated endocytosis (CME) and activity-dependent bulk (ADBE), during mild intense neuronal activity, respectively, to maintain stable neurotransmission. While molecular players modulating CME are well characterized, factors regulating ADBE mechanisms coordinating activations remain poorly understood. Here we report that Minibrain/DYRK1A (Mnb), a kinase mutated in autism up-regulated Down’s syndrome, plays novel role suppressing ADBE. We demonstrate Mnb, together with calcineurin, delicately coordinates by controlling the phosphoinositol phosphatase activity synaptojanin (Synj) varying synaptic demands. Functional domain analyses reveal Synj’s 5′-phosphoinositol suppresses ADBE, while SAC1 is required for efficient Consequently, Parkinson’s disease mutation impairs These data identify Mnb Synj as regulators further indicate differentially governed dual domains.
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