title: TMEM203 Is a Novel Regulator of Intracellular Calcium Homeostasis and Is Required for Spermatogenesis.
abstract: Intracellular calcium signaling is critical for initiating and sustaining diverse cellular functions including transcription, synaptic signaling, muscle contraction, apoptosis and fertilization. Trans-membrane 203 (TMEM203) was identified here in cDNA overexpression screens for proteins capable of modulating intracellular calcium levels using activation of a calcium/calcineurin regulated transcription factor as an indicator. Overexpression of TMEM203 resulted in a reduction of Endoplasmic Reticulum (ER) calcium stores and elevation in basal cytoplasmic calcium levels. TMEM203 protein was localized to the ER and found associated with a number of ER proteins which regulate ER calcium entry and efflux. Mouse Embryonic Fibroblasts (MEFs) derived from Tmem203 deficient mice had reduced ER calcium stores and altered calcium homeostasis. Tmem203 deficient mice were viable though male knockout mice were infertile and exhibited a severe block in spermiogenesis and spermiation. Expression profiling studies showed significant alternations in expression of calcium channels and pumps in testes and concurrently Tmem203 deficient spermatocytes demonstrated significantly altered calcium handling. Thus Tmem203 is an evolutionarily conserved regulator of cellular calcium homeostasis, is required for spermatogenesis and provides a causal link between intracellular calcium regulation and spermiogenesis.
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Prashant B
authors.initials: PB
authors.lastname: Shambharkar
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Bittinger
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Brian
authors.initials: B
authors.lastname: Latario
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: ZhaoHui
authors.initials: Z
authors.lastname: Xiong
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Somnath
authors.initials: S
authors.lastname: Bandyopadhyay
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Davis
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: Lin
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Reginald
authors.initials: R
authors.lastname: Valdez
authors.affiliation: Novartis Institutes for Biomedical Research, Developmental and Molecular Pathways, 100 Technology Square, Cambridge, Massachusetts, United States of America.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Labow
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D007248:Infertility, Male / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding; D013091:Spermatogenesis; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D008565:Membrane Proteins; C000605314:TMEM203 protein, human; D014157:Transcription Factors; D019703:Calcineurin; D002118:Calcium