دورية أكاديمية
Interplay between hevin, SPARC, and MDGAs: Modulators of neurexin-neuroligin transsynaptic bridges.
| العنوان: | Interplay between hevin, SPARC, and MDGAs: Modulators of neurexin-neuroligin transsynaptic bridges. |
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| المؤلفون: | Fan S; Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA., Gangwar SP; Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA., Machius M; Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA., Rudenko G; Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555, USA; Sealy Center for Structural Biology and Molecular Biophysics, University of Texas Medical Branch, Galveston, TX 77555, USA. Electronic address: garudenk@utmb.edu. |
| المصدر: | Structure (London, England : 1993) [Structure] 2021 Jul 01; Vol. 29 (7), pp. 664-678.e6. Date of Electronic Publication: 2021 Feb 02. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101087697 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-4186 (Electronic) Linking ISSN: 09692126 NLM ISO Abbreviation: Structure Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2000- : Cambridge, Mass. : Cell Press Original Publication: London : Current Biology, c1993- |
| مواضيع طبية MeSH: | Calcium-Binding Proteins/*chemistry , Calcium-Binding Proteins/*metabolism , Extracellular Matrix Proteins/*chemistry , Extracellular Matrix Proteins/*metabolism , Nerve Tissue Proteins/*metabolism , Neural Cell Adhesion Molecules/*metabolism , Osteonectin/*chemistry , Osteonectin/*metabolism, Binding Sites ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Domains ; Protein Interaction Maps |
| مستخلص: | Hevin is secreted by astrocytes and its synaptogenic effects are antagonized by the related protein, SPARC. Hevin stabilizes neurexin-neuroligin transsynaptic bridges in vivo. A third protein, membrane-tethered MDGA, blocks these bridges. Here, we reveal the molecular underpinnings of a regulatory network formed by this trio of proteins. The hevin FS-EC structure differs from SPARC, in that the EC domain appears rearranged around a conserved core. The FS domain is structurally conserved and it houses nanomolar affinity binding sites for neurexin and neuroligin. SPARC also binds neurexin and neuroligin, competing with hevin, so its antagonist action is rooted in its shortened N-terminal region. Strikingly, the hevin FS domain competes with MDGA for an overlapping binding site on neuroligin, while the hevin EC domain binds the extracellular matrix protein collagen (like SPARC), so that this trio of proteins can regulate neurexin-neuroligin transsynaptic bridges and also extracellular matrix interactions, impacting synapse formation and ultimately neural circuits. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 Elsevier Ltd. All rights reserved.) |
| التعليقات: | Comment in: Structure. 2021 Jul 1;29(7):635-637. (PMID: 34214438) |
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| معلومات مُعتمدة: | R01 MH077303 United States MH NIMH NIH HHS |
| فهرسة مساهمة: | Keywords: MDGAs; SPARC; adhesion molecule; hevin; matricellular protein; neurexins; neuroligins; neuropsychiatric disease; protein structure; synaptic organizer |
| المشرفين على المادة: | 0 (Calcium-Binding Proteins) 0 (Extracellular Matrix Proteins) 0 (Nerve Tissue Proteins) 0 (Neural Cell Adhesion Molecules) 0 (Osteonectin) 0 (SPARC protein, human) 0 (SPARCL1 protein, human) |
| تواريخ الأحداث: | Date Created: 20210203 Date Completed: 20220111 Latest Revision: 20220716 |
| رمز التحديث: | 20240829 |
| مُعرف محوري في PubMed: | PMC8254758 |
| DOI: | 10.1016/j.str.2021.01.003 |
| PMID: | 33535026 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1878-4186 |
|---|---|
| DOI: | 10.1016/j.str.2021.01.003 |