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Merck
  • Rab4A organizes endosomal domains for sorting cargo to lysosome-related organelles.

Rab4A organizes endosomal domains for sorting cargo to lysosome-related organelles.

Journal of cell science (2018-08-30)
Sudeshna Nag, Shikha Rani, Sarmistha Mahanty, Christin Bissig, Pooja Arora, Cristina Azevedo, Adolfo Saiardi, Peter van der Sluijs, Cedric Delevoye, Guillaume van Niel, Graca Raposo, Subba Rao Gangi Setty
摘要

Sorting endosomes (SEs) are the regulatory hubs for sorting cargo to multiple organelles, including lysosome-related organelles, such as melanosomes in melanocytes. In parallel, melanosome biogenesis is initiated from SEs with the processing and sequential transport of melanocyte-specific proteins toward maturing melanosomes. However, the mechanism of cargo segregation on SEs is largely unknown. Here, RNAi screening in melanocytes revealed that knockdown of Rab4A results in defective melanosome maturation. Rab4A-depletion increases the number of vacuolar endosomes and disturbs the cargo sorting, which in turn lead to the mislocalization of melanosomal proteins to lysosomes, cell surface and exosomes. Rab4A localizes to the SEs and forms an endosomal complex with the adaptor AP-3, the effector rabenosyn-5 and the motor KIF3, which possibly coordinates cargo segregation on SEs. Consistent with this, inactivation of rabenosyn-5, KIF3A or KIF3B phenocopied the defects observed in Rab4A-knockdown melanocytes. Further, rabenosyn-5 was found to associate with rabaptin-5 or Rabip4/4' (isoforms encoded by Rufy1) and differentially regulate cargo sorting from SEs. Thus, Rab4A acts a key regulator of cargo segregation on SEs.This article has an associated First Person interview with the first author of the paper.

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抗γ-微管蛋白抗体,小鼠单克隆 小鼠抗, clone GTU-88, ascites fluid
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酵母营养缺陷型培养基补充剂, without histidine, leucine, and tryptophan