Distinct retrograde microtubule motor sets drive early and late endosome transport. (20th November 2020)

• Record Type: Journal Article
• Authors: Villari, Giulia; Enrico Bena, Chiara; Del Giudice, Marco; Gioelli, Noemi; Sandri, Chiara; Camillo, Chiara; Fiorio Pla, Alessandra; Bosia, Carla; Serini, Guido
• Is Part Of: EMBO journal. Volume 39:Number 24(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-11-20
• Subjects: endoplasmic reticulum -- motor -- movement -- traffic -- vesicles; Molecular biology -- Periodicals; 572.805
• DOI: 10.15252/embj.2019103661
• Languages: English
• ISSNs: 0261-4189

Abstract

Abstract: Although subcellular positioning of endosomes significantly impacts on their functions, the molecular mechanisms governing the different steady‐state distribution of early endosomes (EEs) and late endosomes (LEs)/lysosomes (LYs) in peripheral and perinuclear eukaryotic cell areas, respectively, are still unsolved. We unveil that such differences arise because, while LE retrograde transport depends on the dynein microtubule (MT) motor only, the one of EEs requires the cooperative antagonism of dynein and kinesin‐14 KIFC1, a MT minus end‐directed motor involved in cancer progression. Mechanistically, the Ser‐x‐Ile‐Pro (SxIP) motif‐mediated interaction of the endoplasmic reticulum transmembrane protein stromal interaction molecule 1 (STIM1) with the MT plus end‐binding protein 1 (EB1) promotes its association with the p150Glued subunit of the dynein activator complex dynactin and the distinct location of EEs and LEs/LYs. The peripheral distribution of EEs requires their p150Glued‐mediated simultaneous engagement with dynein and SxIP motif‐containing KIFC1, via HOOK1 and HOOK3 adaptors, respectively. In sum, we provide evidence that distinct minus end‐directed MT motor systems drive the differential transport and subcellular distribution of EEs and LEs in mammalian cells. SYNOPSIS: Distinct subcellular distribution of early and late endosomes is relevant for their specific functions. Here, motor proteins dynein and kinesin KIFC1 are found to be differentially required for retrograde transport of early endosomes vs late endosome/lysosomes towards microtubule (MT) minus ends. Endoplasmic reticulum transmembrane protein STIM1 interacts with MT plus‐end protein EB1 and the p150Glued subunit of dynactin/dynein via its SxIP motif and coiled coil domains. The STIM1/p150Glued/dynein complex drives accumulation of late endosomes in the perinuclear area of the cell. Correct cytosolic distribution of early endosomes depends on their simultaneous engagement with the STIM1/p150Glued/dynein and SxIP motif‐containing KIFC1/p150Glued complexes. HOOK1 and HOOK3 adaptors mediate the interaction of p150Glued with early endosome‐engaged dynein and KIFC1, respectively. Abstract : Differential engagement of STIM1/dynein and the kinesin‐14 KIF1C motor protein complexes regulates distinct subcellular distribution of early and late endosomes.