Article
Multidisciplinary Sciences
Lei Wan, Xi Chen, Wolfhard Almers
Summary: Syntaxin plays a crucial role in catalyzing membrane fusion during exocytosis and forms clusters in the plasma membrane. The mechanism of cluster formation differs between on-granule and off-granule clusters in live PC12 cells.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Vanilla (Hua) Shi, Tim J. Craig, Paul Bishop, Yasuko Nakamura, Dan Rocca, Kevin A. Wilkinson, Jeremy M. Henley
Summary: This study reveals that CK2α over-expression reduces evoked synaptic vesicle release, while knockdown of CK2α enhances vesicle exocytosis from the reserve pool, and a phosphorylation-deficient mutant also increases vesicle exocytosis, indicating a previously unsuspected role of CK2α phosphorylation in regulating the reserve synaptic vesicle pool.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biology
Julia Hesselbarth, Carla Schmidt
Summary: The SNARE complex is composed of vesicular Synaptobrevin-2, Syntaxin-1, and SNAP25, and it mediates fusion between synaptic vesicles and the presynaptic plasma membrane. This study investigates the stepwise assembly of the SNARE complex and its interactions with Complexin-1 using native mass spectrometry and chemical cross-linking. The results provide insights into the stoichiometry of intermediates and off-pathway complexes, as well as the regulation of complex assembly by Complexin-1.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Md Mostafizur Rahman, Asmita Pathak, Kathryn L. Schueler, Haifa Alsharif, Ava Michl, Justin Alexander, Jeong-A Kim, Sushant Bhatnagar
Summary: Stimulus-coupled insulin secretion involves fusion of insulin granules to the plasma membrane via SNARE complex formation. Deletion of Syt9 protein increases glucose clearance and plasma insulin levels in mice. Syt9 interacts with tomosyn-1 and Stx1A, and its inhibitory effects on insulin secretion are mediated by tomosyn-1.
Article
Biochemistry & Molecular Biology
Md Mostafizur Rahman, Asmita Pathak, Kathryn L. Schueler, Haifa Alsharif, Ava Michl, Justin Alexander, Jeong-A Kim, Sushant Bhatnagar
Summary: This study shows that the deletion of Synaptotagmin-9 (Syt9) in mice increases glucose clearance and plasma insulin levels, inhibiting insulin secretion and glucose clearance.
Article
Cell Biology
Guoyi Yang, Liuju Li, Yanmei Liu, Kuo Liang, Lisi Wei, Liangyi Chen
Summary: Impaired insulin release in type 2 diabetes is closely related to chronically elevated glucose concentrations. This study found that high glucose delays fusion events, reduces full fusion, and decreases the size of fusion pores, all contributing to compromised insulin secretion.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Fan Fan, Yumei Wu, Manami Hara, Adam Rizk, Chen Ji, Dan Nerad, Natalia Tamarina, Xuelin Lou
Summary: This study revealed the crucial role of dynamins in endocytosis and secretion capacity of pancreatic beta cells, indicating that deficiency in dynamin-mediated endocytosis can lead to impaired insulin secretion, increasing the risk of endocrine dysfunction and diabetes.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Adam D. Hines, Bruno van Swinderen
Summary: This study develops a method to track the mobility of individual proteins in the entire Drosophila brain, providing a new approach to understanding protein dynamics in neurons. Experimental findings show that different anesthetics affect syntaxin1A molecule mobility differently, which is significant for studying neural activation and inhibition effects.
Review
Biochemistry & Molecular Biology
Najeeb Ullah, Ezzouhra El Maaiden, Md Sahab Uddin, Ghulam Md Ashraf
Summary: This review focuses on the role of the Syt-1 protein in secretory vesicle docking, priming, and fusion. It highlights how Syt-1 acts as a Ca2+ sensor and participates in forming the docking complex to facilitate vesicle fusion with the plasma membrane.
CURRENT PROTEIN & PEPTIDE SCIENCE
(2021)
Article
Cell Biology
Masataka Kunii, Yuria Noguchi, Shin-ichiro Yoshimura, Satoshi Kanda, Tomohiko Iwano, Erda Avriyanti, Nur Atik, Takashi Sato, Ken Sato, Masaharu Ogawa, Akihiro Harada
Summary: In developing brain, the SNARE complex composed of SNAP23, VAMP8, and Syntaxin1B plays a crucial role in the formation of apical junctional complexes (AJCs) and radial glial cell (RGC) polarization. Its depletion leads to severe hypoplasia of the neocortex, absence of hippocampus or cerebellum, loss of RGC polarity, and alterations in proliferation, differentiation, and apoptosis. The localization of AJC protein N-cadherin by SNAREs is essential for AJC formation and RGC polarization during brain development.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Cell Biology
Dhriti P. Shah, Madhavi Joshi, Urja Shedaliya, Amee Krishnakumar
Summary: Glycemic regulation is vital for maintaining physiological functions, and extreme variations in glucose levels can disrupt insulin secretion and lead to hypoglycemia. Neurexin and Neuroligin proteins indirectly influence glycemic levels by regulating insulin secretion. However, the impact of glycemic fluctuations on these docking proteins and their effect on the docking machinery remains unclear. Our study demonstrates decreased expression of Neurexin-1, Neuroligin-2, and Mint-1 during hyperglycemia, hypoglycemia, and diabetic hypoglycemia in rodents and MIN6 cells. We also observed reduced functional insulin secretory granules and morphological changes due to hypoglycemia in control and diabetic conditions, indicating weakened vesicular anchorage and impaired insulin secretion. This is the first report to demonstrate how hypoglycemic events weaken insulin vesicular anchorage in normal and diabetic individuals, highlighting the potential diabetic complications.
CELLULAR SIGNALLING
(2023)
Article
Biochemistry & Molecular Biology
Isabelle Schrauwen, Amama Ghaffar, Thashi Bharadwaj, Khadim Shah, Sakina Rehman, Anushree Acharya, Khurram Liaqat, Nicole S. Lin, Jenna L. Everard, Anwar Khan, Zubair M. Ahmed, Wasim Ahmad, Saima Riazuddin, Suzanne M. Leal
Summary: In this study, a genetic variant in the STX4 gene was found to be associated with congenital hearing impairment. The dysfunction of STX4 was shown to lead to hearing impairment in humans and zebrafish, highlighting its evolutionary conserved role in inner ear development and hair cell functioning.
HUMAN MOLECULAR GENETICS
(2023)
Article
Cell Biology
Wei Liu, Matjaz Stenovec, William Lee, Vedrana Montana, Marko Kreft, Robert Zorec, Vladimir Parpura
Summary: The interactive mechanical forces between individual SNARE proteins Sb2 and Sx1A are sufficient to mediate vesicle docking, suggesting that a trans binary Sx1A-Sb2 complex alone can play a crucial role in the cellular environment.
Article
Biochemistry & Molecular Biology
Undurti N. Das
Summary: Syntaxin regulates pancreatic beta cell mass and participates in insulin secretion. Arachidonic acid (AA) enhances cell membrane fluidity, increases GLUT expression and has anti-inflammatory effects, while prostaglandin E2 (PGE2) activates hypothalamic inflammation and inhibits insulin secretion. Administration of AA and DHA may prevent diabetes.
LIPIDS IN HEALTH AND DISEASE
(2022)
Article
Multidisciplinary Sciences
Volodymyr Petrenko, Nikhil R. Gandasi, Daniel Sage, Anders Tengholm, Sebastian Barg, Charna Dibner
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2020)
Article
Multidisciplinary Sciences
Muhmmad Omar-Hmeadi, Per-Eric Lund, Nikhil R. Gandasi, Anders Tengholm, Sebastian Barg
NATURE COMMUNICATIONS
(2020)
Article
Chemistry, Multidisciplinary
Amir Hatamie, Lin Ren, Haiqiang Dou, Nikhil R. Gandasi, Patrik Rorsman, Andrew Ewing
Summary: The research shows that vesicular release in pancreatic beta cells is not all-or-none, but rather partial release of insulin and serotonin. Utilizing nanoscale amperometric chemical methods, the study quantified the amount of serotonin stored and released during each exocytosis event, revealing that beta cells only release one-third of their granule content. This has implications for understanding type-2 diabetes.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Biochemistry & Molecular Biology
Nikhil R. Gandasi, Vasiliki Arapi, Michel E. Mickael, Prajakta A. Belekar, Louise Granlund, Lakshmi Kothegala, Robert Fredriksson, Sonchita Bagchi
Summary: SLC38A6 (SNAT6) is a transporter expressed exclusively in excitatory neurons of the brain, with high specificity for glutamine and glutamate. It forms complexes with caveolin on the plasma membrane to aid in its sodium dependent trafficking. Potential interacting partners identified include CTP synthase 2, phosphate activated glutaminase, and glutamate metabotropic receptor 2.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biotechnology & Applied Microbiology
Diego Balboa, Tom Barsby, Vaino Lithovius, Jonna Saarimaki-Vire, Muhmmad Omar-Hmeadi, Oleg Dyachok, Hossam Montaser, Per-Eric Lund, Mingyu Yang, Hazem Ibrahim, Anna Naatanen, Vikash Chandra, Helena Vihinen, Eija Jokitalo, Jouni Kvist, Jarkko Ustinov, Anni I. Nieminen, Emilia Kuuluvainen, Ville Hietakangas, Pekka Katajisto, Joey Lau, Per-Ola Carlsson, Sebastian Barg, Anders Tengholm, Timo Otonkoski
Summary: Transplanting pancreatic islet cells derived from human pluripotent stem cells has great potential for treating diabetes. This study generated functionally mature stem-cell-derived islets (SC-islets) using an optimized protocol and compared them comprehensively to primary adult islets. The results showed that SC-islets exhibited similar functional properties to adult islets in terms of insulin secretion, electrophysiology, signaling, and exocytosis. Additionally, single-cell transcriptomics revealed a continuous maturation trajectory of SC-islets in vitro and during engraftment in mice, closely resembling that of primary islets.
NATURE BIOTECHNOLOGY
(2022)
Article
Multidisciplinary Sciences
Ewelina Golec, Alexander Ekstrom, Maciej Noga, Muhmmad Omar-Hmeadi, Per-Eric Lund, Bruno O. Villoutreix, Ulrika Krus, Katarzyna Wozniak, Olle Korsgren, Erik Renstrom, Sebastian Barg, Ben C. King, Anna M. Blom
Summary: The study finds that splice variants of CD59 exist in human and mouse pancreatic islets. These variants are associated with insulin granules and insulin secretion. In type 2 diabetes patients, the expression of these variants is significantly reduced, which may contribute to insulin deficiency.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Review
Biochemistry & Molecular Biology
Aishwarya A. Makam, Anusmita Biswas, Lakshmi Kothegala, Nikhil R. Gandasi
Summary: Type-1-diabetes (T1D) is primarily an autoimmune disorder where pancreatic beta-cells are unable to secrete sufficient insulin, leading to elevated blood glucose levels. The development and pathogenesis of T1D involve a complex interplay of various risk factors, including genetic, environmental, and cellular elements. In this context, ER stress and its consequences, such as defective protein processing and autoantigen generation, play a crucial role in T1D development and beta-cell destruction.
Article
Cell Biology
Muhmmad Omar-Hmeadi, Alenka Gucek, Sebastian Barg
Summary: Phosphatidylinositol(4,5)bisphosphate (PI(4,5)P2) is a crucial phospholipid in regulated exocytosis and some forms of endocytosis. The accumulation of PI(4,5)P2 at the release site inhibits fusion pore expansion and cargo release through an unconventional endocytic mechanism. This process involves the recruitment of endocytic fission machinery and is independent of clathrin-mediated endocytosis.
Article
Multidisciplinary Sciences
Yu-Te Yeh, Chandan Sona, Xin Yan, Yunxiao Li, Adrija Pathak, Mark I. McDermott, Zhigang Xie, Liangwen Liu, Anoop Arunagiri, Yuting Wang, Amaury Cazenave-Gassiot, Adhideb Ghosh, Ferdinand von Meyenn, Sivarajan Kumarasamy, Sonia M. Najjar, Shiqi Jia, Markus R. Wenk, Alexis Traynor-Kaplan, Peter Arvan, Sebastian Barg, Vytas A. Bankaitis, Matthew N. Poy
Summary: Type 2 diabetes (T2D) is characterized by pancreatic beta-cell failure. Restoration of Phosphatidylinositol transfer protein alpha (PITPNA) in T2D islets reverses impaired insulin granule maturation, exocytosis, and ER stress. PITPNA deficiency accompanies beta-cell dysfunction in T2D.
NATURE COMMUNICATIONS
(2023)
Article
Endocrinology & Metabolism
Nikhil R. Gandasi, Rui Gao, Lakshmi Kothegala, Abigail Pearce, Cristiano Santos, Samuel Acreman, Davide Basco, Anna Benrick, Margarita V. Chibalina, Anne Clark, Claudia Guida, Matthew Harris, Paul R. V. Johnson, Jakob G. Knudsen, Jinfang Ma, Caroline Miranda, Makoto Shigeto, Andrei I. Tarasov, Ho Yan Yeung, Bernard Thorens, Ingrid W. Asterholm, Quan Zhang, Reshma Ramracheya, Graham Ladds, Patrik Rorsman
Summary: The GLP-1 metabolite GLP-1(9-36) is a systemic inhibitor of glucagon secretion, and this mechanism is impaired in diabetes.
Review
Biochemistry & Molecular Biology
Muhmmad Omar-Hmeadi, Olof Idevall-Hagren
Summary: This article reviews the process of insulin biosynthesis, storage, and release, as well as the role of beta cells in the development of diabetes. Studies have found that insulin granules undergo various complex regulatory mechanisms during their formation, maturation, transport, and release.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)