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Full-Text Articles in Medical Molecular Biology
Extended-Synaptotagmin-1 And -2 Control T Cell Signaling And Function, Nathalia Benavides, Claudio G. Giraudo
Extended-Synaptotagmin-1 And -2 Control T Cell Signaling And Function, Nathalia Benavides, Claudio G. Giraudo
Department of Microbiology and Immunology Faculty Papers
Upon T-cell activation, the levels of the secondary messenger diacylglycerol (DAG) at the plasma membrane need to be controlled to ensure appropriate T-cell receptor signaling and T-cell functions. Extended-Synaptotagmins (E-Syts) are a family of inter-organelle lipid transport proteins that bridge the endoplasmic reticulum and the plasma membrane. In this study, we identify a novel regulatory mechanism of DAG-mediated signaling for T-cell effector functions based on E-Syt proteins. We demonstrate that E-Syts downmodulate T-cell receptor signaling, T-cell-mediated cytotoxicity, degranulation, and cytokine production by reducing plasma membrane levels of DAG. Mechanistically, E-Syt2 predominantly modulates DAG levels at the plasma membrane in resting-state …
Steady-State Regulation Of Secretory Cargo Export And Er Homeostasis By Inositol Trisphosphate Receptors And Penta-Ef-Hand Proteins, Aaron J. Held
Steady-State Regulation Of Secretory Cargo Export And Er Homeostasis By Inositol Trisphosphate Receptors And Penta-Ef-Hand Proteins, Aaron J. Held
Graduate Student Theses, Dissertations, & Professional Papers
Constant protein degradation and turnover necessitates constitutive secretion that delivers the correct mix of nascent proteins to their appropriate subcellular destinations. Cells thus exhibit steady-state secretion and the additional ability to adjust secretory flux, though we lack a clear understanding of this critical process. During secretion, the COPII coat is responsible for providing a balance of actively and passively selected ER cargos to enter the secretory pathway. Furthermore, Ca2+ -binding proteins have been implicated in regulating this process in response to Ca2+ signals. In Chapter 1, we review the secretory pathway and vesicular trafficking, with a focus on …