TMEM203 Is a Novel Regulator of Intracellular Calcium Homeostasis and Is Required for Spermatogenesis
| Autor: | Mark Labow, Somnath Bandyopadhyay, Vanessa Davis, ZhaoHui Xiong, Yi Yang, Mark Bittinger, Brian Jude Latario, Reginald Valdez, Victor Lin, Prashant Shambharkar |
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| Rok vydání: | 2015 |
| Předmět: |
Male
medicine.medical_specialty Intracellular Space lcsh:Medicine Gene Expression chemistry.chemical_element Biology Calcium Endoplasmic Reticulum Calcium in biology Cell Line Mice Internal medicine medicine Animals Homeostasis Humans Calcium Signaling lcsh:Science Spermatogenesis Infertility Male Calcium signaling Epididymis Mice Knockout Calcium metabolism Multidisciplinary Voltage-dependent calcium channel Ryanodine receptor Calcineurin lcsh:R Membrane Proteins Cell biology Endocrinology Gene Expression Regulation chemistry lcsh:Q Female Synaptic signaling medicine.symptom Research Article Protein Binding Transcription Factors Muscle contraction |
| Zdroj: | PLoS ONE PLoS ONE, Vol 10, Iss 5, p e0127480 (2015) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0127480 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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