title: Melanoregulin regulates retrograde melanosome transport through interaction with the RILP-p150Glued complex in melanocytes.
abstract: Melanoregulin (Mreg), a product of the dilute suppressor gene, has been implicated in the regulation of melanosome transport in mammalian epidermal melanocytes, given that Mreg deficiency was found to restore peripheral melanosome distribution from perinuclear melanosome aggregation in Rab27A-deficient melanocytes. However, the function of Mreg in melanosome transport has remained unclear. Here, we show that Mreg regulates microtubule-dependent retrograde melanosome transport through the dynein-dynactin motor complex. Mreg interacted with the C-terminal domain of Rab-interacting lysosomal protein (RILP) and formed a complex with RILP and p150(Glued) (also known as dynactin subunit 1, DCTN1), a component of the dynein-dynactin motor complex, in cultured cells. Overexpression of Mreg, RILP or both, in normal melanocytes induced perinuclear melanosome aggregation, whereas knockdown of Mreg or functional disruption of the dynein-dynactin motor complex restored peripheral melanosome distribution in Rab27A-deficient melanocytes. These findings reveal a new mechanism by which the dynein-dynactin motor complex recognizes Mreg on mature melanosomes through interaction with RILP and is involved in the centripetal movement of melanosomes.
authors.affiliation: Laboratory of Membrane Trafficking Mechanisms, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi 980-8578, Japan. nori@m.tohoku.ac.jp
authors.forename: Norihiko
authors.initials: N
authors.lastname: Ohbayashi
authors.forename: Yuto
authors.initials: Y
authors.lastname: Maruta
authors.forename: Morié
authors.initials: M
authors.lastname: Ishida
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Fukuda
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002461:Cell Line, Transformed; D000072159:Dynactin Complex; D047908:Intracellular Signaling Peptides and Proteins; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D020460:Melanosomes / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; C000606364:Dctn1 protein, mouse; D000072159:Dynactin Complex; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C498920:Rilp protein, mouse; C518334:melanoregulin protein, mouse