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Multiple C 2 domains transmembrane protein 1 is expressed in CNS neurons and possibly regulates cellular vesicle retrieval and oxidative stress
Author(s) -
Qiu Lifeng,
Yu Hanry,
Liang Fengyi
Publication year - 2015
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13251
Subject(s) - biology , microbiology and biotechnology , synaptic vesicle , synaptic vesicle recycling , endosome , dentate gyrus , transmembrane protein , immunocytochemistry , neuroscience , vesicle , hippocampus , biochemistry , endocrinology , intracellular , receptor , membrane
Multiple C 2 domains transmembrane protein 1 ( MCTP 1) contains two transmembrane regions and three C 2 domains of high Ca 2+ ‐binding affinity. Single‐nucleotide polymorphism ( SNP ) of human MCTP 1 gene is reportedly associated with bipolar disorder, but expression and function of MCTP 1 in the CNS is still largely unknown. We cloned rat MCTP 1 isoforms, and studied expression of MCTP 1 transcript and protein in the CNS . Subcellular distribution and functional roles of MCTP 1 were investigated in cultured primary neurons or PC 12 cells by over‐expression, cell imaging, and flow cytometry. MCTP 1 immunostaining was seen in both CNS neuronal cell bodies and processes, especially in the hippocampus, dentate gyrus, medial habenular nucleus, amygdala, and selected cerebral and cerebellar cortical areas/layers. Under an electron microscope, MCTP 1 immunoreactivity was observed on vesicles in neuronal cell bodies and pre‐synaptic axon terminals. In cultured primary neurons and PC 12 cells MCTP 1 was detected on selected populations of secretory vesicles and endosomes. MCTP 1 over‐expression significantly inhibited neuronal transferrin endocytosis, secretory vesicle retrieval, cell migration, and oxidative stress from glutamate toxicity. Thus MCTP 1 might be involved in regulating endocytic recycling of specific CNS neurons and synapses. MCTP 1 abnormality might cause altered synaptic vesicle recycling, and thereby lead to vulnerability to neuropsychiatric diseases.MCTP1 in the CNS is a neuronal vesicle/endosome protein. Mutation or expression variation of MCTP1 has been associated with neuropsychiatric disorders. The present in vivo and in vitro imaging studies demonstrated vesicular localization of MCTP1 on the endocytic recycling pathway. Functional assays indicated involvement of MCTP1 in multiple cellular functions including endocytosis, cell migration and anti‐excitotoxicity in neuronal cells.