title: T Cell Receptor Mediated Calcium Entry Requires Alternatively Spliced Cav1.1 Channels.
abstract: The process of calcium entry in T cells is a multichannel and multi-step process. We have studied the requirement for L-type calcium channels (Cav1.1) α1S subunits during calcium entry after TCR stimulation. High expression levels of Cav1.1 channels were detected in activated T cells. Sequencing and cloning of Cav1.1 channel cDNA from T cells revealed that a single splice variant is expressed. This variant lacks exon 29, which encodes the linker region adjacent to the voltage sensor, but contains five new N-terminal exons that substitute for exons 1 and 2, which are found in the Cav1.1 muscle counterpart. Overexpression studies using cloned T cell Cav1.1 in 293HEK cells (that lack TCR) suggest that the gating of these channels was altered. Knockdown of Cav1.1 channels in T cells abrogated calcium entry after TCR stimulation, suggesting that Cav1.1 channels are controlled by TCR signaling.
authors.affiliation: Department of Natural Sciences, The Open University of Israel, 1 University Road, Ra'anana, 4353701, Israel.
authors.forename: Didi
authors.initials: D
authors.lastname: Matza
authors.affiliation: Genetic and Molecular Pathology Laboratory, Casablanca School of Medicine and Pharmacy, Hassan II University, Casablanca, Morocco.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Badou
authors.affiliation: Virginia Tech Applied Research Corporation, 900 North Glebe Road, Arlington, VA, 22203, United States of America.
authors.forename: Kathryn G
authors.initials: KG
authors.lastname: Klemic
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, 300 Cedar street, New Haven, CT, 06520, United States of America.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, 06520, United States of America.
authors.forename: Judith
authors.initials: J
authors.lastname: Stein
authors.affiliation: Yale Center for Clinical Investigation, Yale University School of Medicine, New Haven, CT, 06520, United States of America.
authors.forename: Usha
authors.initials: U
authors.lastname: Govindarajulu
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical center, Boston, MA, 02215, United States of America.
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Nadler
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical center, Boston, MA, 02215, United States of America.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kinet
authors.affiliation: Goldyne Savad Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, 91120, Israel.
authors.forename: Amnon
authors.initials: A
authors.lastname: Peled
authors.affiliation: Department of Cardiothoracic Surgery, Hadassah University Hospital, Jerusalem, 91120, Israel.
authors.forename: Oz M
authors.initials: OM
authors.lastname: Shapira
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT, 06520, United States of America.|Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT, 06520, United States of America.
authors.forename: Leonard K
authors.initials: LK
authors.lastname: Kaczmarek
authors.affiliation: Department of Immunobiology, Yale University School of Medicine, 300 Cedar street, New Haven, CT, 06520, United States of America.|Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT, 06520, United States of America.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000378:metabolism*; D005091:Exons; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D012326:RNA Splicing; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*
chemical_list: C529218:CACNA1S protein, mouse; D020746:Calcium Channels, L-Type; D011948:Receptors, Antigen, T-Cell; D002118:Calcium
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