Background: Synaptotagmin proteins were first identified in nervous tissue, residing in synaptic vesicles. Synaptotagmins were subsequently found to form a large family, some members of which play important roles in calcium triggered exocytic events. These members have been investigated intensively, but other family members are not well understood, making it difficult to grasp the meaning of family membership in functional terms. Further difficulty arises as families are defined quite legitimately in different ways: by common descent or by common possession of distinguishing features. One definition does not necessarily imply the other. The evolutionary range of genome sequences now available, can shed more light on synaptotagmin gene phylogeny and clarify family relationships. The aim of compiling this open access collection of synaptotagmin and synaptotagmin-like sequences, is that its use may lead to greater understanding of the biological function of these proteins in an evolutionary context.
Results: 46 metazoan genomes were examined and their complement of Syt, Esyt, Rph3a, Rph3al, Doc2 and Dblc2 genes identified. All of the sequences were compared, named, then examined in detail. Esyt genes were formerly named Fam62. The species in this collection are Trichoplax, Nematostella, Capitella, Helobdella, Lottia, Ciona, Strongylocentrotus, Branchiostoma, Ixodes, Daphnia, Acyrthosiphon, Tribolium, Nasonia, Apis, Anopheles, Drosophila, Caenorhabditis, Takifugu, Tetraodon, Gasterosteus, Oryzias, Danio, Xenopus, Anolis, Gallus, Taeniopygia,Ornithorhynchus, Monodelphis, Mus and Homo. All of the data described in this paper is available as additional files.
Conclusions: Only a subset of synaptotagmin proteins appear able to function as calcium triggers. Syt1, Syt7 and Syt9 are ancient conserved synaptotagmins of this type. Some animals carry extensive repertoires of synaptotagmin genes. Other animals of no less complexity, carry only a small repertoire. Current understanding does not explain why this is so. The biological roles of many synaptotagmins remain to be understood. This collection of genes offers prospects for fruitful speculation about the functional roles of the synaptotagmin repertoires of different animals and includes a great range of biological complexity. With reference to this gene collection, functional relationships among Syt, Esyt, Rph3a, Rph3al, Doc2 and Dblc2 genes, which encode similar proteins, can better be assessed in future.
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http://dx.doi.org/10.1186/1471-2164-11-37 | DOI Listing |
ACS Chem Biol
August 2024
Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York 14853, United States.
The proper distribution of lipids within organelle membranes requires rapid interorganelle lipid transport, much of which occurs at membrane contact sites and is mediated by lipid transfer proteins (LTPs). Our current understanding of LTP mechanism and function is based largely on structural studies and in vitro reconstitution. Existing cellular assays for LTP function use indirect readouts, and it remains an open question as to whether substrate specificity and transport kinetics established in vitro are similar in cellular settings.
View Article and Find Full Text PDFUpon 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.
View Article and Find Full Text PDFFront Cell Dev Biol
November 2023
Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, Hebei, China.
Membrane contact sites (MCSs) are adjacent locations between the membranes of two different organelles and play important roles in various physiological processes, including cellular calcium and lipid signaling. In cancer research, MCSs have been proposed to regulate tumor metabolism and fate, contributing to tumor progression, and this function could be exploited for tumor therapy. However, there is little evidence on how MCSs are involved in cancer progression.
View Article and Find Full Text PDFJ Cell Sci
August 2023
Department of Neurophysiology, Institute of Physiology and Pathophysiology, Philipps University Marburg, 35037 Marburg, Germany.
Nat Commun
March 2023
State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Frontiers Science Center for Cell Responses, Nankai University, Tianjin, China.
The Synaptotagmin-like Mitochondrial-lipid-binding Protein (SMP) domain is a newly identified lipid transfer module present in proteins that regulate lipid homeostasis at membrane contact sites (MCSs). However, how the SMP domain associates with the membrane to extract and unload lipids is unclear. Here, we performed in vitro DNA brick-assisted lipid transfer assays and in silico molecular dynamics simulations to investigate the molecular basis of the membrane association by the SMP domain of extended synaptotagmin (E-Syt), which tethers the tubular endoplasmic reticulum (ER) to the plasma membrane (PM).
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!