{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:06:16Z","timestamp":1783721176136,"version":"3.55.0"},"reference-count":44,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T00:00:00Z","timestamp":1554336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Argentine Science Agency","award":["PICT 2012-2116 and 2016-1851"],"award-info":[{"award-number":["PICT 2012-2116 and 2016-1851"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rab GTPases define the identity and destiny of vesicles. Some of these small GTPases present isoforms that are expressed differentially along developmental stages or in a tissue-specific manner, hence comparative analysis is difficult to achieve. Here, we describe the intracellular distribution and function in lipid transport of the poorly characterized Rab39 isoforms using typical cell biology experimental tools and new ones developed in our laboratory. We show that, despite their amino acid sequence similarity, Rab39a and Rab39b display non-overlapping intracellular distribution. Rab39a localizes in the late endocytic pathway, mainly at multivesicular bodies. In contrast, Rab39b distributes in the secretory network, at the endoplasmic reticulum\/cis-Golgi interface. Therefore, Rab39a controls trafficking of lipids (sphingomyelin and phospholipids) segregated at multivesicular bodies, whereas Rab39b transports sphingolipids biosynthesized at the endoplasmic reticulum-Golgi factory. Interestingly, lyso bis-phosphatidic acid is exclusively transported by Rab39a, indicating that both isoforms do not exert identical functions in lipid transport. Conveniently, the requirement of eukaryotic lipids by the intracellular pathogen Chlamydia trachomatis rendered useful for dissecting and distinguishing Rab39a- and Rab39b-controlled trafficking pathways. Our findings provide comparative insights about the different subcellular distribution and function in lipid transport of the two Rab39 isoforms.<\/jats:p>","DOI":"10.3390\/ijms20071688","type":"journal-article","created":{"date-parts":[[2019,4,4]],"date-time":"2019-04-04T11:31:57Z","timestamp":1554377517000},"page":"1688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Rab39a and Rab39b Display Different Intracellular Distribution and Function in Sphingolipids and Phospholipids Transport"],"prefix":"10.3390","volume":"20","author":[{"given":"Juli\u00e1n","family":"Gambarte Tudela","sequence":"first","affiliation":[{"name":"Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Ciudad de Mendoza, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Buonfigli","sequence":"additional","affiliation":[{"name":"Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Ciudad de Mendoza, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Luj\u00e1n","sequence":"additional","affiliation":[{"name":"Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Ciudad de Mendoza, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariano","family":"Alonso Bivou","sequence":"additional","affiliation":[{"name":"Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Ciudad de Mendoza, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ignacio","family":"Cebri\u00e1n","sequence":"additional","affiliation":[{"name":"Instituto de Histolog\u00eda y Embriolog\u00eda de Mendoza (IHEM, Universidad Nacional de Cuyo, CONICET), Facultad de Ciencias M\u00e9dicas, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anah\u00ed","family":"Capmany","sequence":"additional","affiliation":[{"name":"Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Ciudad de Mendoza, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Damiani","sequence":"additional","affiliation":[{"name":"Biochemistry and Immunity Laboratory, School of Medicine, University of Cuyo, IMBECU-CONICET, Centro Universitario, Ciudad de Mendoza, Mendoza 5500, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1038\/nrm2728","article-title":"Rab GTPases as coordinators of vesicle traffic","volume":"10","author":"Stenmark","year":"2009","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/35052055","article-title":"Rab proteins as membrane organizers","volume":"2","author":"Zerial","year":"2001","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"a022616","DOI":"10.1101\/cshperspect.a022616","article-title":"Rab proteins and the compartmentalization of the endosomal system","volume":"6","author":"Zerial","year":"2014","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1016\/S0006-291X(03)00482-0","article-title":"Rab39, a novel Golgi-associated Rab GTPase from human dendritic cells involved in cellular endocytosis","volume":"303","author":"Chen","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1111\/j.1600-0854.2011.01165.x","article-title":"Rab GTPases regulating phagosome maturation are differentially recruited to mycobacterial phagosomes","volume":"12","author":"Seto","year":"2011","journal-title":"Traffic"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"34531","DOI":"10.1074\/jbc.M109.046102","article-title":"Rab39a binds caspase-1 and is required for caspase-1-dependent interleukin-1beta secretion","volume":"284","author":"Becker","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1159\/000064047","article-title":"Isolation and characterization of a human novel RAB (RAB39B) gene","volume":"97","author":"Cheng","year":"2002","journal-title":"Cytogenet. Genome Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2907.e11-2","DOI":"10.1016\/j.neurobiolaging.2015.06.019","article-title":"Genetic analysis of the RAB39B gene in Chinese Han patients with Parkinson\u2019s disease","volume":"36","author":"Yuan","year":"2015","journal-title":"Neurobiol. Aging"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/humu.22497","article-title":"Increased dosage of RAB39B affects neuronal development and could explain the cognitive impairment in male patients with distal Xq28 copy number gains","volume":"35","author":"Vanmarsenille","year":"2014","journal-title":"Hum. Mutat."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.ajhg.2014.10.015","article-title":"Mutations in RAB39B cause X-linked intellectual disability and early-onset Parkinson disease with \u03b1-synuclein pathology","volume":"95","author":"Wilson","year":"2014","journal-title":"Am. J. Hum. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1080\/21541248.2016.1212688","article-title":"C9ORF72 is a GDP\/GTP exchange factor for Rab8 and Rab39 and regulates autophagy","volume":"8","author":"Corbier","year":"2017","journal-title":"Small GTPases"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6504","DOI":"10.1038\/ncomms7504","article-title":"The intellectual disability protein RAB39B selectively regulates GluA2 trafficking to determine synaptic AMPAR composition","volume":"6","author":"Mignogna","year":"2015","journal-title":"Nat. Commun."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Yao, Y., Cui, X., Al-Ramahi, I., Sun, X., Li, B., Hou, J., Difiglia, M., Palacino, J., Wu, Z.-Y., and Ma, L. (2015). A striatal-enriched intronic GPCR modulates huntingtin levels and toxicity. eLife.","DOI":"10.7554\/eLife.05449"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1083\/jcb.201008051","article-title":"Family-wide characterization of the DENN domain Rab GDP-GTP exchange factors","volume":"191","author":"Yoshimura","year":"2010","journal-title":"J. Cell Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5241","DOI":"10.1016\/j.febslet.2006.08.053","article-title":"Rab14 is part of the early endosomal clathrin-coated TGN microdomain","volume":"580","author":"Gaugel","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1128\/IAI.00917-13","article-title":"New frontiers in type III secretion biology: The Chlamydia perspective","volume":"82","author":"Mueller","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1038\/nrmicro.2016.30","article-title":"Chlamydia cell biology and pathogenesis","volume":"14","author":"Elwell","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1010","DOI":"10.1111\/j.1462-5822.2012.01794.x","article-title":"Lipid acquisition by intracellular Chlamydiae","volume":"14","author":"Elwell","year":"2012","journal-title":"Cell. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.mib.2009.11.002","article-title":"Acquisition of nutrients by Chlamydiae: Unique challenges of living in an intracellular compartment","volume":"13","author":"Saka","year":"2010","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1111\/cmi.12325","article-title":"Targeting eukaryotic Rab proteins: A smart strategy for chlamydial survival and replication","volume":"16","author":"Damiani","year":"2014","journal-title":"Cell. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1034\/j.1600-0854.2000.010201.x","article-title":"Redirection of host vesicle trafficking pathways by intracellular parasites","volume":"1","author":"Hackstadt","year":"2000","journal-title":"Traffic"},{"key":"ref_22","first-page":"3068","article-title":"The late endocytic Rab39a GTPase regulates the interaction between multivesicular bodies and chlamydial inclusions","volume":"128","author":"Capmany","year":"2015","journal-title":"J. Cell Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5362","DOI":"10.1128\/IAI.00539-06","article-title":"The GTPase Rab4 interacts with Chlamydia trachomatis inclusion membrane protein CT229","volume":"74","author":"Rzomp","year":"2006","journal-title":"Infect. Immun."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/cmi.12035","article-title":"Rab11-family of interacting protein 2 associates with chlamydial inclusions through its Rab-binding domain and promotes bacterial multiplication","volume":"15","author":"Leiva","year":"2013","journal-title":"Cell. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"5855","DOI":"10.1128\/IAI.71.10.5855-5870.2003","article-title":"Rab GTPases are recruited to chlamydial inclusions in both a species-dependent and species-independent manner","volume":"71","author":"Rzomp","year":"2003","journal-title":"Infect. Immun."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rejman Lipinski, A., Heymann, J., Meissner, C., Karlas, A., Brinkmann, V., Meyer, T.F., and Heuer, D. (2009). Rab6 and Rab11 regulate Chlamydia trachomatis development and golgin-84-dependent Golgi fragmentation. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000615"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Capmany, A., and Damiani, M.T. (2010). Chlamydia trachomatis intercepts Golgi-derived sphingolipids through a Rab14-mediated transport required for bacterial development and replication. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0014084"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1091\/mbc.e13-05-0236","article-title":"Identification and characterization of multiple novel Rab\u2013myosin Va interactions","volume":"24","author":"Lindsay","year":"2013","journal-title":"Mol. Biol. Cell"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1146\/annurev.cellbio.23.090506.123319","article-title":"Biogenesis and Function of Multivesicular Bodies","volume":"23","author":"Piper","year":"2007","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/jb\/mvj128","article-title":"Exosomes: A Common Pathway for a Specialized Function","volume":"140","author":"Simoes","year":"2006","journal-title":"J. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.bbamcr.2018.07.009","article-title":"Rab and Arf proteins at the crossroad between membrane transport and cytoskeleton dynamics","volume":"1865","author":"Kjos","year":"2018","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1042\/BST0391179","article-title":"The role of motor proteins in endosomal sorting","volume":"39","author":"Hunt","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/bs.mcb.2015.05.004","article-title":"Rab GTPases and kinesin motors in endosomal trafficking","volume":"130","author":"Delevoye","year":"2015","journal-title":"Methods Cell Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1042\/BST0391202","article-title":"Rab GTPases and microtubule motors","volume":"39","author":"Horgan","year":"2011","journal-title":"Biochem. Soc. Trans."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3601","DOI":"10.1529\/biophysj.104.054874","article-title":"Spatiotemporal Image Correlation Spectroscopy (STICS) Theory, Verification, and Application to Protein Velocity Mapping in Living CHO Cells","volume":"88","author":"Hebert","year":"2005","journal-title":"Biophys. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/S0014-4827(03)00340-9","article-title":"Rab11b resides in a vesicular compartment distinct from Rab11a in parietal cells and other epithelial cells","volume":"290","author":"Lapierre","year":"2003","journal-title":"Exp. Cell Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0014-5793(95)00477-Q","article-title":"Co-operative regulation of endocytosis by three Rab5 isoforms","volume":"366","author":"Bucci","year":"1995","journal-title":"FEBS Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"30328","DOI":"10.1074\/jbc.M109.034546","article-title":"Rab5 isoforms differentially regulate the trafficking and degradation of epidermal growth factor receptors","volume":"284","author":"Chen","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1111\/tra.12083","article-title":"Rab27 effectors, pleiotropic regulators in secretory pathways","volume":"14","author":"Fukuda","year":"2013","journal-title":"Traffic"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ncb2000","article-title":"Rab27a and Rab27b control different steps of the exosome secretion pathway","volume":"12","author":"Ostrowski","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6559","DOI":"10.1074\/jbc.M115.712760","article-title":"Rab8b Regulates Transport of West Nile Virus Particles from Recycling Endosomes","volume":"291","author":"Kobayashi","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6771","DOI":"10.1073\/pnas.1131289100","article-title":"Golgi-dependent transport of cholesterol to the Chlamydia trachomatis inclusion","volume":"100","author":"Carabeo","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"9379","DOI":"10.1073\/pnas.0712241105","article-title":"Cytoplasmic lipid droplets are translocated into the lumen of the Chlamydia trachomatis parasitophorous vacuole","volume":"105","author":"ZL","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/B978-0-12-391857-4.00009-4","article-title":"Methods for Cell and Particle Tracking","volume":"504","author":"Meijering","year":"2012","journal-title":"Methods Enzymol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/7\/1688\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:42:58Z","timestamp":1760186578000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/20\/7\/1688"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,4]]},"references-count":44,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["ijms20071688"],"URL":"https:\/\/doi.org\/10.3390\/ijms20071688","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,4]]}}}