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- Miller Lab: Role of Vinculin in Tricellular Junctions
- Jakob Lab: Embryonic Stem Cell Fate
- Wierzbicki Lab: Membrane association of active genes organizes the chloroplast nucleoid structure
- Shan Lab: Dual phosphorylation of DGK5-mediated PA burst regulates ROS in plant immunity
- Simmons Lab: Bacillus subtilis encodes a discrete flap endonuclease that cleaves RNA-DNA hybrids
- DeSantis/Nandakumar Labs: KASH5 protein
- Cadigan Lab: SOX9 and TCF transcription factors associate to mediate Wnt/β-catenin target gene activation in colorectal cancer
DeSantis/Nandakumar Labs: KASH5 protein
DeSantis/Nandakumar Labs: The KASH5 protein involved in meiotic chromosomal movements is a novel dynein activating adaptor
Ritvija Agrawal, John P Gillies, Juliana L Zang, Jingjing Zhang, Sharon R Garrott, Hiroki Shibuya, Jayakrishnan Nandakumar, Morgan E DeSantis
Dynein harnesses ATP hydrolysis to move cargo on microtubules in multiple biological contexts. Dynein meets a unique challenge in meiosis by moving chromosomes tethered to the nuclear envelope to facilitate homolog pairing essential for gametogenesis. Though processive dynein motility requires binding to an activating adaptor, the identity of the activating adaptor required for dynein to move meiotic chromosomes is unknown. We show that the meiosis-specific nuclear-envelope protein KASH5 is a dynein activating adaptor: KASH5 directly binds dynein using a mechanism conserved among activating adaptors and converts dynein into a processive motor. We map the dynein-binding surface of KASH5, identifying mutations that abrogate dynein binding in vitro and disrupt recruitment of the dynein machinery to the nuclear envelope in cultured cells and mouse spermatocytes in vivo. Our study identifies KASH5 as the first transmembrane dynein activating adaptor and provides molecular insights into how it activates dynein during meiosis.