Seminar: "Dynamin-1: a vesicle fission protein or more than that?" by Dr. Satyajit Mahapatra

Speaker: Dr. Satyajit Mahapatra

Title: " Dynamin-1: a vesicle fission protein or more than that?"

Abstract:
Dynamin-1 is a large guanosine triphosphatase (GTPase) thought to be critically essential for the fission of synaptic vesicles (SVs) during endocytic recycling¹. Inhibition of dynamin function studies (pharmacologically and by use of mutants) corroborated this idea^1,2,3,4. However, studies on conventional dynamin-1 knockout mice with limited postnatal viability, suggest dynamin-1 is required only during intense synaptic activity but is dispensable for basal endocytic vesicle recycling need^5,6. These contrasting results from dynamin inhibition and knockout studies led us to understand what role does dynamin-1 play in mature, native brain circuits. Using tissue-specific conditional knockout (cKO) of dynamin-1 at the calyx of Held synapses ex-vivo in mice (P16-20) that are normal outwardly, we found ablation of dynamin-1 did not affect the vesicle resupply rate, basal transmission, and the common synaptic properties⁷. However, strong synaptic stimulation for a short⁷, as well as for longer time periods⁸, enhanced the neurotransmitter release^7,8 in cKO. Presynaptic membrane capacitance recordings and other data suggest that greater release in the absence of dynamin-1 was due to enhanced availability of release sites within 500 ms⁷, and increase in the size of SVs within 10s8, both achieved through an augmented actin-dependent endocytic membrane retrieval process^7,8. Thus, implying, in addition to its role in membrane fission, dynamin-1 in native brain circuits may have a role in slowing the endocytosis pace7 to quality control better the size of synaptic vesicles⁸.

References:
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2. Yamashita et al., (2005). Science. 307 (5706): 124 - 127.
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4. Takei et al., (1995). Nature. 374 (6518): 186-90
5. Ferguson et al., (2007). Science. 316 (5824): 570-574
6. Lou et al., (2008). PNAS. 105 (45): 17555-60
7. Mahapatra et al., (2016). PNAS. 113 (22): E3150-8
8. Mahapatra et al., (2017). J.Physiol. 595 (1): 193-206