Symmetrical organization of proteins under docked synaptic vesicles. Issue 2 (18th January 2019)

• Record Type: Journal Article
• Authors: Li, Xia; Radhakrishnan, Abhijith; Grushin, Kirill; Kasula, Ravikiran; Chaudhuri, Arunima; Gomathinayagam, Sujatha; Krishnakumar, Shyam S.; Liu, Jun; Rothman, James E.
• Is Part Of: FEBS letters. Volume 593:Issue 2(2019)
• Page Start: 144
• Page End: 153
• Publication Date: 2019-01-18
• Subjects: cryo‐electron tomography -- PC12 cells -- regulated exocytosis -- SNARE proteins -- synaptotagmin; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13316
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : During calcium‐regulated exocytosis, the constitutive fusion machinery is 'clamped' in a partially assembled state until synchronously released by calcium. The protein machinery involved in this process is known, but the supra ‐molecular architecture and underlying mechanisms are unclear. Here, we use cryo‐electron tomography analysis in nerve growth factor‐differentiated neuro‐endocrine (PC12) cells to delineate the organization of the release machinery under the docked vesicles. We find that exactly six exocytosis modules, each likely consisting of a single SNAREpin with its bound Synaptotagmins, Complexin, and Munc18 proteins, are symmetrically arranged at the vesicle–PM interface. Mutational analysis suggests that the symmetrical organization is templated by circular oligomers of Synaptotagmin. The observed arrangement, including its precise radial positioning, is in‐line with the recently proposed 'buttressed ring hypothesis'. Abstract :