Bakker Nina, Jongsma Marlieke L M, Neefjes Jacques
Department of Cell and Chemical Biology and Oncode Institute, Leiden University Medical Center, Leiden, Netherlands.
Front Cell Dev Biol. 2025 Jun 16;13:1575571. doi: 10.3389/fcell.2025.1575571. eCollection 2025.
Late endosomes/lysosomes (LE/Lys) and lysosome related organelles (LROs) move dynamically through cells which involves many levels of regulation. To reach their destination, they need to connect to the motor proteins dynein-dynactin, kinesin or myosin for long-range bidirectional transport along microtubules and short-range movement along actin filaments. This connection depends on various factors at the microtubule, including the MAP- and tubulin-code, as well as adaptors, Rab GTPases and effector proteins marking the LE/Lys and LRO membranes. Mutations affecting this transport results in defective LE/Lys or LRO cargo delivery often resulting in skin, neurological and/or immunological diseases. How LE/Lys and LRO transport is orchestrated and how it fails in disease states, will be discussed.
晚期内体/溶酶体(LE/Lys)和溶酶体相关细胞器(LROs)在细胞中动态移动,这涉及多个层次的调控。为了到达目的地,它们需要与动力蛋白动力蛋白激活蛋白复合物、驱动蛋白或肌球蛋白连接,以便沿着微管进行长距离双向运输,并沿着肌动蛋白丝进行短距离移动。这种连接取决于微管上的各种因素,包括微管相关蛋白和微管蛋白编码,以及标记LE/Lys和LRO膜的衔接蛋白、Rab GTP酶和效应蛋白。影响这种运输的突变会导致LE/Lys或LRO货物递送缺陷,常常导致皮肤、神经和/或免疫疾病。本文将讨论LE/Lys和LRO运输是如何协调的,以及在疾病状态下它是如何失效的。