The Recycling Endosome Protein Rab17 Regulates Melanocytic Filopodia Formation and Melanosome Trafficking
Rab GTPases including Rab27a, Rab38 and Rab32 function in melanosome maturation or trafficking in melanocytes. A screen to identify additional Rabs involved in these processes revealed the localization of GFP‐Rab17 on recycling endosomes (REs) and melanosomes in melanocytic cells. Rab17 mRNA express...
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| Veröffentlicht in: | Traffic (Copenhagen, Denmark) Denmark), 2011-05, Vol.12 (5), p.627-643 |
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| creator | Beaumont, Kimberley A. Hamilton, Nicholas A. Moores, Matthew T. Brown, Darren L. Ohbayashi, Norihiko Cairncross, Oliver Cook, Anthony L. Smith, Aaron G. Misaki, Ryo Fukuda, Mitsunori Taguchi, Tomohiko Sturm, Richard A. Stow, Jennifer L. |
| description | Rab GTPases including Rab27a, Rab38 and Rab32 function in melanosome maturation or trafficking in melanocytes. A screen to identify additional Rabs involved in these processes revealed the localization of GFP‐Rab17 on recycling endosomes (REs) and melanosomes in melanocytic cells. Rab17 mRNA expression is regulated by microphthalmia transcription factor (MITF), a characteristic of known pigmentation genes. Rab17 siRNA knockdown in melanoma cells quantitatively increased melanosome concentration at the cell periphery. Rab17 knockdown did not inhibit melanosome maturation nor movement, but it caused accumulation of melanin inside cells. Double knockdown of Rab17 and Rab27a indicated that Rab17 acts on melanosomes downstream of Rab27a. Filopodia are known to play a role in melanosome transfer, and in Rab17 knockdown cells filopodia formation was inhibited. Furthermore, we show that stimulation of melanoma cells with α‐melanocyte‐stimulating hormone induces filopodia formation, supporting a role for filopodia in melanosome release. Cell stimulation also caused redistribution of REs to the periphery, and knockdown of additional RE‐associated Rabs 11a and 11b produced a similar accumulation of melanosomes and melanin to that seen after loss of Rab17. Our findings reveal new functions for RE and Rab17 in pigmentation through a distal step in the process of melanosome release via filopodia. |
| doi_str_mv | 10.1111/j.1600-0854.2011.01172.x |
| format | Article |
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A screen to identify additional Rabs involved in these processes revealed the localization of GFP‐Rab17 on recycling endosomes (REs) and melanosomes in melanocytic cells. Rab17 mRNA expression is regulated by microphthalmia transcription factor (MITF), a characteristic of known pigmentation genes. Rab17 siRNA knockdown in melanoma cells quantitatively increased melanosome concentration at the cell periphery. Rab17 knockdown did not inhibit melanosome maturation nor movement, but it caused accumulation of melanin inside cells. Double knockdown of Rab17 and Rab27a indicated that Rab17 acts on melanosomes downstream of Rab27a. Filopodia are known to play a role in melanosome transfer, and in Rab17 knockdown cells filopodia formation was inhibited. Furthermore, we show that stimulation of melanoma cells with α‐melanocyte‐stimulating hormone induces filopodia formation, supporting a role for filopodia in melanosome release. Cell stimulation also caused redistribution of REs to the periphery, and knockdown of additional RE‐associated Rabs 11a and 11b produced a similar accumulation of melanosomes and melanin to that seen after loss of Rab17. Our findings reveal new functions for RE and Rab17 in pigmentation through a distal step in the process of melanosome release via filopodia.</description><identifier>ISSN: 1398-9219</identifier><identifier>EISSN: 1600-0854</identifier><identifier>DOI: 10.1111/j.1600-0854.2011.01172.x</identifier><identifier>PMID: 21291502</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>alpha-MSH - pharmacology ; Animals ; Biomarkers - metabolism ; Cell Line, Tumor ; Endosomes - metabolism ; filopodia ; Gene Knockdown Techniques ; Humans ; melanin ; Melanins - metabolism ; melanocyte ; Melanocytes - cytology ; Melanocytes - drug effects ; Melanocytes - metabolism ; melanosome ; Melanosomes - metabolism ; Mice ; Microphthalmia-Associated Transcription Factor - genetics ; Microphthalmia-Associated Transcription Factor - metabolism ; MITF ; Pseudopodia - metabolism ; Pseudopodia - ultrastructure ; rab GTP-Binding Proteins - genetics ; rab GTP-Binding Proteins - metabolism ; Rab11 ; Rab17 ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - metabolism ; recycling endosome ; RNA, Small Interfering - metabolism</subject><ispartof>Traffic (Copenhagen, Denmark), 2011-05, Vol.12 (5), p.627-643</ispartof><rights>2011 John Wiley & Sons A/S</rights><rights>2011 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4342-2c6a1a960e67fda60527371fd0b8b2621f1577bbb865373fdf52d1024cb56a1f3</citedby><cites>FETCH-LOGICAL-c4342-2c6a1a960e67fda60527371fd0b8b2621f1577bbb865373fdf52d1024cb56a1f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fj.1600-0854.2011.01172.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fj.1600-0854.2011.01172.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,1427,27901,27902,45550,45551,46384,46808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21291502$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Beaumont, Kimberley A.</creatorcontrib><creatorcontrib>Hamilton, Nicholas A.</creatorcontrib><creatorcontrib>Moores, Matthew T.</creatorcontrib><creatorcontrib>Brown, Darren L.</creatorcontrib><creatorcontrib>Ohbayashi, Norihiko</creatorcontrib><creatorcontrib>Cairncross, Oliver</creatorcontrib><creatorcontrib>Cook, Anthony L.</creatorcontrib><creatorcontrib>Smith, Aaron G.</creatorcontrib><creatorcontrib>Misaki, Ryo</creatorcontrib><creatorcontrib>Fukuda, Mitsunori</creatorcontrib><creatorcontrib>Taguchi, Tomohiko</creatorcontrib><creatorcontrib>Sturm, Richard A.</creatorcontrib><creatorcontrib>Stow, Jennifer L.</creatorcontrib><title>The Recycling Endosome Protein Rab17 Regulates Melanocytic Filopodia Formation and Melanosome Trafficking</title><title>Traffic (Copenhagen, Denmark)</title><addtitle>Traffic</addtitle><description>Rab GTPases including Rab27a, Rab38 and Rab32 function in melanosome maturation or trafficking in melanocytes. A screen to identify additional Rabs involved in these processes revealed the localization of GFP‐Rab17 on recycling endosomes (REs) and melanosomes in melanocytic cells. Rab17 mRNA expression is regulated by microphthalmia transcription factor (MITF), a characteristic of known pigmentation genes. Rab17 siRNA knockdown in melanoma cells quantitatively increased melanosome concentration at the cell periphery. Rab17 knockdown did not inhibit melanosome maturation nor movement, but it caused accumulation of melanin inside cells. Double knockdown of Rab17 and Rab27a indicated that Rab17 acts on melanosomes downstream of Rab27a. Filopodia are known to play a role in melanosome transfer, and in Rab17 knockdown cells filopodia formation was inhibited. Furthermore, we show that stimulation of melanoma cells with α‐melanocyte‐stimulating hormone induces filopodia formation, supporting a role for filopodia in melanosome release. Cell stimulation also caused redistribution of REs to the periphery, and knockdown of additional RE‐associated Rabs 11a and 11b produced a similar accumulation of melanosomes and melanin to that seen after loss of Rab17. Our findings reveal new functions for RE and Rab17 in pigmentation through a distal step in the process of melanosome release via filopodia.</description><subject>alpha-MSH - pharmacology</subject><subject>Animals</subject><subject>Biomarkers - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Endosomes - metabolism</subject><subject>filopodia</subject><subject>Gene Knockdown Techniques</subject><subject>Humans</subject><subject>melanin</subject><subject>Melanins - metabolism</subject><subject>melanocyte</subject><subject>Melanocytes - cytology</subject><subject>Melanocytes - drug effects</subject><subject>Melanocytes - metabolism</subject><subject>melanosome</subject><subject>Melanosomes - metabolism</subject><subject>Mice</subject><subject>Microphthalmia-Associated Transcription Factor - genetics</subject><subject>Microphthalmia-Associated Transcription Factor - metabolism</subject><subject>MITF</subject><subject>Pseudopodia - metabolism</subject><subject>Pseudopodia - ultrastructure</subject><subject>rab GTP-Binding Proteins - genetics</subject><subject>rab GTP-Binding Proteins - metabolism</subject><subject>Rab11</subject><subject>Rab17</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - metabolism</subject><subject>recycling endosome</subject><subject>RNA, Small Interfering - metabolism</subject><issn>1398-9219</issn><issn>1600-0854</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkE9PwyAYh4nROJ1-BcPNUyu8Lf1z8LAsm5rMaJZ5JpTCZLZlli5u3166zZ0lIbwJz-8HeRDClITUr4dVSBNCApKxOARCaeh3CuH2DF2dLs79HOVZkAPNB-jauRUhBFgcX6IBUMgpI3CFzOJT4bmSO1mZZoknTWmdrRV-b22nTIPnoqCpB5abSnTK4VdVicbKXWcknprKrm1pBJ7athadsQ0WTXlk9jWLVmht5JfvvkEXWlRO3R7PIfqYThbj52D29vQyHs0CGUcxBCATQUWeEJWkuhQJYZBGKdUlKbICEqCasjQtiiJLWJRGutQMSkoglgXzSR0N0f2hd93a741yHa-Nk6ryf1J243iWUCARMPBkdiBla51rlebr1tSi3XFKeO-Zr3ivk_c6ee-Z7z3zrY_eHR_ZFLUqT8E_sR54PAA_plK7fxfzxXzUT9EvlOaLwA</recordid><startdate>201105</startdate><enddate>201105</enddate><creator>Beaumont, Kimberley A.</creator><creator>Hamilton, Nicholas A.</creator><creator>Moores, Matthew T.</creator><creator>Brown, Darren L.</creator><creator>Ohbayashi, Norihiko</creator><creator>Cairncross, Oliver</creator><creator>Cook, Anthony L.</creator><creator>Smith, Aaron G.</creator><creator>Misaki, Ryo</creator><creator>Fukuda, Mitsunori</creator><creator>Taguchi, Tomohiko</creator><creator>Sturm, Richard A.</creator><creator>Stow, Jennifer L.</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201105</creationdate><title>The Recycling Endosome Protein Rab17 Regulates Melanocytic Filopodia Formation and Melanosome Trafficking</title><author>Beaumont, Kimberley A. ; Hamilton, Nicholas A. ; Moores, Matthew T. ; Brown, Darren L. ; Ohbayashi, Norihiko ; Cairncross, Oliver ; Cook, Anthony L. ; Smith, Aaron G. ; Misaki, Ryo ; Fukuda, Mitsunori ; Taguchi, Tomohiko ; Sturm, Richard A. ; Stow, Jennifer L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4342-2c6a1a960e67fda60527371fd0b8b2621f1577bbb865373fdf52d1024cb56a1f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>alpha-MSH - pharmacology</topic><topic>Animals</topic><topic>Biomarkers - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Endosomes - metabolism</topic><topic>filopodia</topic><topic>Gene Knockdown Techniques</topic><topic>Humans</topic><topic>melanin</topic><topic>Melanins - metabolism</topic><topic>melanocyte</topic><topic>Melanocytes - cytology</topic><topic>Melanocytes - drug effects</topic><topic>Melanocytes - metabolism</topic><topic>melanosome</topic><topic>Melanosomes - metabolism</topic><topic>Mice</topic><topic>Microphthalmia-Associated Transcription Factor - genetics</topic><topic>Microphthalmia-Associated Transcription Factor - metabolism</topic><topic>MITF</topic><topic>Pseudopodia - metabolism</topic><topic>Pseudopodia - ultrastructure</topic><topic>rab GTP-Binding Proteins - genetics</topic><topic>rab GTP-Binding Proteins - metabolism</topic><topic>Rab11</topic><topic>Rab17</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - metabolism</topic><topic>recycling endosome</topic><topic>RNA, Small Interfering - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Beaumont, Kimberley A.</creatorcontrib><creatorcontrib>Hamilton, Nicholas A.</creatorcontrib><creatorcontrib>Moores, Matthew T.</creatorcontrib><creatorcontrib>Brown, Darren L.</creatorcontrib><creatorcontrib>Ohbayashi, Norihiko</creatorcontrib><creatorcontrib>Cairncross, Oliver</creatorcontrib><creatorcontrib>Cook, Anthony L.</creatorcontrib><creatorcontrib>Smith, Aaron G.</creatorcontrib><creatorcontrib>Misaki, Ryo</creatorcontrib><creatorcontrib>Fukuda, Mitsunori</creatorcontrib><creatorcontrib>Taguchi, Tomohiko</creatorcontrib><creatorcontrib>Sturm, Richard A.</creatorcontrib><creatorcontrib>Stow, Jennifer L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Traffic (Copenhagen, Denmark)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beaumont, Kimberley A.</au><au>Hamilton, Nicholas A.</au><au>Moores, Matthew T.</au><au>Brown, Darren L.</au><au>Ohbayashi, Norihiko</au><au>Cairncross, Oliver</au><au>Cook, Anthony L.</au><au>Smith, Aaron G.</au><au>Misaki, Ryo</au><au>Fukuda, Mitsunori</au><au>Taguchi, Tomohiko</au><au>Sturm, Richard A.</au><au>Stow, Jennifer L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Recycling Endosome Protein Rab17 Regulates Melanocytic Filopodia Formation and Melanosome Trafficking</atitle><jtitle>Traffic (Copenhagen, Denmark)</jtitle><addtitle>Traffic</addtitle><date>2011-05</date><risdate>2011</risdate><volume>12</volume><issue>5</issue><spage>627</spage><epage>643</epage><pages>627-643</pages><issn>1398-9219</issn><eissn>1600-0854</eissn><abstract>Rab GTPases including Rab27a, Rab38 and Rab32 function in melanosome maturation or trafficking in melanocytes. A screen to identify additional Rabs involved in these processes revealed the localization of GFP‐Rab17 on recycling endosomes (REs) and melanosomes in melanocytic cells. Rab17 mRNA expression is regulated by microphthalmia transcription factor (MITF), a characteristic of known pigmentation genes. Rab17 siRNA knockdown in melanoma cells quantitatively increased melanosome concentration at the cell periphery. Rab17 knockdown did not inhibit melanosome maturation nor movement, but it caused accumulation of melanin inside cells. Double knockdown of Rab17 and Rab27a indicated that Rab17 acts on melanosomes downstream of Rab27a. Filopodia are known to play a role in melanosome transfer, and in Rab17 knockdown cells filopodia formation was inhibited. Furthermore, we show that stimulation of melanoma cells with α‐melanocyte‐stimulating hormone induces filopodia formation, supporting a role for filopodia in melanosome release. Cell stimulation also caused redistribution of REs to the periphery, and knockdown of additional RE‐associated Rabs 11a and 11b produced a similar accumulation of melanosomes and melanin to that seen after loss of Rab17. Our findings reveal new functions for RE and Rab17 in pigmentation through a distal step in the process of melanosome release via filopodia.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>21291502</pmid><doi>10.1111/j.1600-0854.2011.01172.x</doi><tpages>17</tpages></addata></record> |
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| ispartof | Traffic (Copenhagen, Denmark), 2011-05, Vol.12 (5), p.627-643 |
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| source | Wiley Free Content; MEDLINE; IngentaConnect Free/Open Access Journals; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | alpha-MSH - pharmacology Animals Biomarkers - metabolism Cell Line, Tumor Endosomes - metabolism filopodia Gene Knockdown Techniques Humans melanin Melanins - metabolism melanocyte Melanocytes - cytology Melanocytes - drug effects Melanocytes - metabolism melanosome Melanosomes - metabolism Mice Microphthalmia-Associated Transcription Factor - genetics Microphthalmia-Associated Transcription Factor - metabolism MITF Pseudopodia - metabolism Pseudopodia - ultrastructure rab GTP-Binding Proteins - genetics rab GTP-Binding Proteins - metabolism Rab11 Rab17 Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - metabolism recycling endosome RNA, Small Interfering - metabolism |
| title | The Recycling Endosome Protein Rab17 Regulates Melanocytic Filopodia Formation and Melanosome Trafficking |
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