题 目：Load-dependent assembly of multi-dynein complexes enhances force generation

主 讲：Arne Gennerich 教授（阿尔伯特·爱因斯坦医学院）

时 间：2026年8月18日（周二）10:30-11:30

地 点：学习书坊（琳恩图书馆二楼）

报告摘要：

Cytoplasmic dynein drives long-distance transport along microtubules, but how a single motor complex adapts to the mechanical loads it encounters in cells has remained an open question. I will present our discovery that the dynein-dynactin-BicD2 (DDB) complex is not a fixed machine but a load-responsive assembly that changes composition under force. Using optical trapping, multi-color single-molecule fluorescence, and structural approaches, we show that DDB recruits a third dynein under mechanical tension through an auxiliary BicD2 adaptor, forming a tri-dynein complex that nearly doubles the force output of the two-dynein state. This recruitment is gated by Lis1, which prevents force-limiting autoinhibited conformations and increases load-bearing capacity. Our findings establish a new principle in motor biology: that a cytoskeletal motor adapts to load by dynamically changing its stoichiometry, the first such demonstration for any motor protein. These results reframe intracellular transport as an emergent, mechanosensitive process in which motor number, not just motor properties, is tuned to match mechanical demand.

嘉宾简介：

Arne Gennerich is a professor of Biochemistry at the Albert Einstein College of Medicine in New York. He received his Ph.D. in Biophysics from the University of Göttingen, Germany, and completed postdoctoral training in Ronald Vale's laboratory at the University of California, San Francisco. His research combines single-molecule biophysics, optical tweezers, and structural biology to elucidate the mechanisms of cytoskeletal motor proteins, including dynein and kinesins, and to understand how disease-associated mutations disrupt intracellular transport. Dr. Gennerich has published extensively in leading journals such as Cell, Nature Cell Biology, Nature Communications, and Science Advances, and currently leads multiple NIH-funded research programs on molecular motor mechanisms and neurological disease.