title: STX13 regulates cargo delivery from recycling endosomes during melanosome biogenesis.
abstract: Melanosomes are a class of lysosome-related organelles produced by melanocytes. Biogenesis of melanosomes requires the transport of melanin-synthesizing enzymes from tubular recycling endosomes to maturing melanosomes. The SNARE proteins involved in these transport or fusion steps have been poorly studied. We found that depletion of syntaxin 13 (STX13, also known as STX12), a recycling endosomal Qa-SNARE, inhibits pigment granule maturation in melanocytes by rerouting the melanosomal proteins such as TYR and TYRP1 to lysosomes. Furthermore, live-cell imaging and electron microscopy studies showed that STX13 co-distributed with melanosomal cargo in the tubular-vesicular endosomes that are closely associated with the maturing melanosomes. STX family proteins contain an N-terminal regulatory domain, and deletion of this domain in STX13 increases both the SNARE activity in vivo and melanosome cargo transport and pigmentation, suggesting that STX13 acts as a fusion SNARE in melanosomal trafficking pathways. In addition, STX13-dependent cargo transport requires the melanosomal R-SNARE VAMP7, and its silencing blocks the melanosome maturation, reflecting a defect in endosome-melanosome fusion. Moreover, we show mutual dependency between STX13 and VAMP7 in regulating their localization for efficient cargo delivery to melanosomes.
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Riddhi Atul
authors.initials: RA
authors.lastname: Jani
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Latha Kallur
authors.initials: LK
authors.lastname: Purushothaman
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India.
authors.forename: Shikha
authors.initials: S
authors.lastname: Rani
authors.affiliation: Institut Curie, Centre de Recherche, Paris 75248, France Structure and Membrane Compartments, and Cell and Tissue Imaging Facility (PICT-IBiSA), CNRS UMR144, Paris 75248, France.
authors.forename: Ptissam
authors.initials: P
authors.lastname: Bergam
authors.affiliation: Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India subba@mcbl.iisc.ernet.in.
authors.forename: Subba Rao Gangi
authors.initials: SR
authors.lastname: Setty
mesh_terms: D000818:Animals; D002460:Cell Line; D011992:Endosomes / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000235:genetics / Q000378:metabolism; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism*; D020460:Melanosomes / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008562:Membrane Glycoproteins; D050765:Qa-SNARE Proteins; C496151:STX12 protein, human; C496153:syntaxin 12, mouse; D010088:Oxidoreductases; C489799:TYRP1 protein, human
keywords: AP-3; HPS; SNARE recycling; STX13; TYR; TYRP1; VAMP7