title: Multiple C2 domains transmembrane protein 1 is expressed in CNS neurons and possibly regulates cellular vesicle retrieval and oxidative stress.
abstract: Multiple C2 domains transmembrane protein 1 (MCTP1) contains two transmembrane regions and three C2 domains of high Ca(2+)-binding affinity. Single-nucleotide polymorphism (SNP) of human MCTP1 gene is reportedly associated with bipolar disorder, but expression and function of MCTP1 in the CNS is still largely unknown. We cloned rat MCTP1 isoforms, and studied expression of MCTP1 transcript and protein in the CNS. Subcellular distribution and functional roles of MCTP1 were investigated in cultured primary neurons or PC12 cells by over-expression, cell imaging, and flow cytometry. MCTP1 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, MCTP1 immunoreactivity was observed on vesicles in neuronal cell bodies and pre-synaptic axon terminals. In cultured primary neurons and PC12 cells MCTP1 was detected on selected populations of secretory vesicles and endosomes. MCTP1 over-expression significantly inhibited neuronal transferrin endocytosis, secretory vesicle retrieval, cell migration, and oxidative stress from glutamate toxicity. Thus MCTP1 might be involved in regulating endocytic recycling of specific CNS neurons and synapses. MCTP1 abnormality might cause altered synaptic vesicle recycling, and thereby lead to vulnerability to neuropsychiatric diseases.
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.|Institute of Bioengineering and Nanotechnology, A*STAR, Singapore, Singapore.|Mechanobiology Institute, Singapore, Singapore.|Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Hanry
authors.initials: H
authors.lastname: Yu
authors.affiliation: Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Fengyi
authors.initials: F
authors.lastname: Liang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002490:Central Nervous System / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018384:Oxidative Stress / Q000502:physiology*; D016716:PC12 Cells; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000502:physiology*
chemical_list: C496709:MCTP1 protein, human; D008565:Membrane Proteins
keywords: multiple C2 domains transmembrane protein 1; neuronal migration; reactive oxygen species; recycling endosome; secretory vesicle; synapse