{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T13:35:34Z","timestamp":1785936934760,"version":"3.56.0"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T00:00:00Z","timestamp":1602201600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Ykt6 is an evolutionarily conserved SNARE protein regulating Golgi membrane fusion and other diverse membrane trafficking pathways. Unlike most SNARE proteins, Ykt6 lacks a transmembrane domain but instead has a tandem cysteine motif at the C-terminus. Recently, we have demonstrated that Ykt6 undergoes double prenylation at the C-terminal two cysteines first by farnesyltransferase and then by a newly identified protein prenyltransferase named geranylgeranyltransferase type-III (GGTase-III). GGTase-III consists of a novel \u03b1 subunit prenyltransferase alpha subunit repeat containing 1 (PTAR1) and the \u03b2 subunit of Rab geranylgeranyltransferase. PTAR1 knockout (KO) cells, where Ykt6 is singly prenylated with a farnesyl moiety, exhibit structural and functional abnormalities in the Golgi apparatus with delayed intra-Golgi trafficking and impaired protein glycosylation. It remains unclear whether the second prenylation of Ykt6 is required for proper trafficking of lysosomal hydrolases from Golgi to lysosomes. Here, we show that lysosomal hydrolases, cathepsin D and \u03b2-hexosaminidase, were missorted at the trans-Golgi network and secreted into the extracellular space in PTAR1 KO cells. Moreover, maturation of these hydrolases was disturbed. LC3B, an autophagy marker, was accumulated in PTAR1 KO cells, suggesting defects in cellular degradation pathways. Thus, doubly prenylated Ykt6, but not singly prenylated Ykt6, is critical for the efficient sorting and trafficking of acid hydrolases to lysosomes.<\/jats:p>","DOI":"10.1093\/jb\/mvaa111","type":"journal-article","created":{"date-parts":[[2020,9,25]],"date-time":"2020-09-25T11:17:04Z","timestamp":1601032624000},"page":"363-370","source":"Crossref","is-referenced-by-count":22,"title":["Double prenylation of SNARE protein Ykt6 is required for lysosomal hydrolase trafficking"],"prefix":"10.1093","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5420-957X","authenticated-orcid":false,"given":"Natsumi","family":"Sakata","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryutaro","family":"Shirakawa","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Goto","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duc Anh","family":"Trinh","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisanori","family":"Horiuchi","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Biology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,10,9]]},"reference":[{"key":"2021041817174055300_mvaa111-B1","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/0092-8674(90)90242-7","article-title":"Inhibition of purified p21ras farnesyl: protein transferase by Cys-AAX tetrapeptides","volume":"62","author":"Reiss","year":"1990","journal-title":"Cell"},{"key":"2021041817174055300_mvaa111-B2","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/0092-8674(91)90460-G","article-title":"Protein farnesyltransferase and geranylgeranyltransferase share a common alpha subunit","volume":"65","author":"Seabra","year":"1991","journal-title":"Cell"},{"key":"2021041817174055300_mvaa111-B3","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/0092-8674(92)90253-9","article-title":"Purification of component A of Rab geranylgeranyl transferase: possible identity with the choroideremia gene product","volume":"70","author":"Seabra","year":"1992","journal-title":"Cell"},{"key":"2021041817174055300_mvaa111-B4","doi-asserted-by":"crossref","first-page":"e104120","DOI":"10.15252\/embj.2019104120","article-title":"A SNARE geranylgeranyltransferase essential for the organization of the Golgi apparatus","volume":"39","author":"Shirakawa","year":"2020","journal-title":"EMBO J"},{"key":"2021041817174055300_mvaa111-B5","doi-asserted-by":"crossref","first-page":"17776","DOI":"10.1074\/jbc.272.28.17776","article-title":"Ykt6p, a prenylated SNARE essential for endoplasmic reticulum-Golgi transport","volume":"272","author":"McNew","year":"1997","journal-title":"J. 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