跳转至内容
Merck
CN

LRRK2 mediates tubulation and vesicle sorting from lysosomes.

Science advances (2020-11-13)
Luis Bonet-Ponce, Alexandra Beilina, Chad D Williamson, Eric Lindberg, Jillian H Kluss, Sara Saez-Atienzar, Natalie Landeck, Ravindran Kumaran, Adamantios Mamais, Christopher K E Bleck, Yan Li, Mark R Cookson
摘要

Genetic variation around the LRRK2 gene affects risk of both familial and sporadic Parkinson's disease (PD). However, the biological functions of LRRK2 remain incompletely understood. Here, we report that LRRK2 is recruited to lysosomes after exposure of cells to the lysosome membrane-rupturing agent LLOME. Using an unbiased proteomic screen, we identified the motor adaptor protein JIP4 as an LRRK2 partner at the lysosomal membrane. LRRK2 can recruit JIP4 to lysosomes in a kinase-dependent manner via the phosphorylation of RAB35 and RAB10. Using super-resolution live-cell imaging microscopy and FIB-SEM, we demonstrate that JIP4 promotes the formation of LAMP1-negative tubules that release membranous content from lysosomes. Thus, we describe a new process orchestrated by LRRK2, which we name LYTL (LYsosomal Tubulation/sorting driven by LRRK2), by which lysosomal tubulation is used to release vesicles from lysosomes. Given the central role of the lysosome in PD, LYTL is likely to be disease relevant.

材料
货号
品牌
产品描述

Sigma-Aldrich
单克隆抗-FLAG® M2 小鼠抗, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Roche
抗-GFP, from mouse IgG1κ (clones 7.1 and 13.1)
Sigma-Aldrich
诺考达唑, ≥99% (TLC), powder
Sigma-Aldrich
亮氨酸-亮氨酸甲酯 氢溴酸盐, ≥97% (TLC)
Supelco
碳酸钠溶液, 0.1 M Na2CO3 in water, eluent concentrate for IC
Sigma-Aldrich
MISSION® esiRNA, targeting human SPAG9