CLN8 explained

Protein CLN8 is a protein that in humans is encoded by the CLN8 gene.^{[1] [2]}

Molecular biology

This gene encodes a transmembrane protein that localizes to the endoplasmic reticulum (ER) and recycles between the ER and the Golgi apparatus via COPII- and COPI-coated vesicles.^[3] CLN8 protein functions as a cargo receptor for lysosomal soluble proteins in the ER.^[4] CLN8 proteins pair with CLN6 proteins to form the EGRESS complex (ER-to-Golgi relaying of enzymes of the lysosomal system), the functional unit responsible for the export of lysosomal enzymes from the endoplasmic reticulum.^[5]

Clinical

Mutations in this gene are associated with progressive epilepsy with mental retardation (EPMR), a subtype of neuronal ceroid lipofuscinosis (NCL). Patients with mutations in this gene have altered levels of sphingolipid and phospholipids in the brain.

Further reading

• Dawson G, Cho S . Batten's disease: clues to neuronal protein catabolism in lysosomes. . J. Neurosci. Res. . 60 . 2 . 133–40 . 2000 . 10740217 . 10.1002/(SICI)1097-4547(20000415)60:2<133::AID-JNR1>3.0.CO;2-3 . 28786470.
• Ranta S, Lehesjoki AE . Northern epilepsy, a new member of the NCL family. . Neurol. Sci. . 21 . 3 Suppl . S43–7 . 2001 . 11073227 . 10.1007/s100720070039 . 11677694.
• Winter E, Ponting CP . TRAM, LAG1 and CLN8: members of a novel family of lipid-sensing domains? . Trends Biochem. Sci. . 27 . 8 . 381–3 . 2002 . 12151215 . 10.1016/S0968-0004(02)02154-0.
• Ranta S . Genetic and physical mapping of the progressive epilepsy with mental retardation (EPMR) locus on chromosome 8p . Genome Res. . 6 . 5 . 351–60 . 1996 . 8743986 . 6145179 . 10.1101/gr.6.5.351 . vanc . Lehesjoki AE . Hirvasniemi A . 3 . Weissenbach . J . Ross . B . Leal . S M . De La Chapelle . A . Gilliam . T C.
• Lonka L . The neuronal ceroid lipofuscinosis CLN8 membrane protein is a resident of the endoplasmic reticulum . Hum. Mol. Genet. . 9 . 11 . 1691–7 . 2000 . 10861296 . 10.1093/hmg/9.11.1691 . vanc . Kyttälä A . Ranta S . 3 . Jalanko . A . Lehesjoki . AE . free.
• Strausberg RL . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . vanc . Feingold EA . Grouse LH . 3 . Derge . JG . Klausner . RD . Collins . FS . Wagner . L . Shenmen . CM . Schuler . GD . 2002PNAS...9916899M . free.
• Verhoeven K . Slowed Conduction and Thin Myelination of Peripheral Nerves Associated with Mutant Rho Guanine-Nucleotide Exchange Factor 10 . Am. J. Hum. Genet. . 73 . 4 . 926–32 . 2003 . 14508709 . 10.1086/378159 . 1180612 . vanc . De Jonghe P . Van de Putte T . 3 . Nelis . Eva . Zwijsen . An . Verpoorten . Nathalie . De Vriendt . Els . Jacobs . An . Van Gerwen . Veerle.
• Ota T . Complete sequencing and characterization of 21,243 full-length human cDNAs . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . vanc . Suzuki Y . Nishikawa T . 3 . Otsuki . Tetsuji . Sugiyama . Tomoyasu . Irie . Ryotaro . Wakamatsu . Ai . Hayashi . Koji . Sato . Hiroyuki . free.
• Ranta S . Variant late infantile neuronal ceroid lipofuscinosis in a subset of Turkish patients is allelic to Northern epilepsy . Hum. Mutat. . 23 . 4 . 300–5 . 2004 . 15024724 . 10.1002/humu.20018 . vanc . Topcu M . Tegelberg S . 3 . Tan . Hüseyin . Üstübütün . Alp . Saatci . Isil . Dufke . Andreas . Enders . Herbert . Pohl . Keith . 34924032 . free.
• Gerhard DS . The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC) . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . vanc . Wagner L . Feingold EA . 3 . Shenmen . CM . Grouse . LH . Schuler . G . Klein . SL . Old . S . Rasooly . R.
• Hermansson M . Mass spectrometric analysis reveals changes in phospholipid, neutral sphingolipid and sulfatide molecular species in progressive epilepsy with mental retardation, EPMR, brain: a case study . J. Neurochem. . 95 . 3 . 609–17 . 2005 . 16086686 . 10.1111/j.1471-4159.2005.03376.x . vanc . Käkelä R . Berghäll M . 3 . Lehesjoki . Anna-Elina . Somerharju . Pentti . Lahtinen . Ulla . 23379785 . free.
• Kimura K . Diversification of transcriptional modulation: Large-scale identification and characterization of putative alternative promoters of human genes . Genome Res. . 16 . 1 . 55–65 . 2006 . 16344560 . 10.1101/gr.4039406 . 1356129 . vanc . Wakamatsu A . Suzuki Y . 3 . Ota . T . Nishikawa . T . Yamashita . R . Yamamoto . J . Sekine . M . Tsuritani . K.

External links

• GeneReviews/NIH/NCBI/UW entry on Neuronal Ceroid-Lipofuscinoses

Notes and References

1. Ranta S, Zhang Y, Ross B, Lonka L, Takkunen E, Messer A, Sharp J, Wheeler R, Kusumi K, Mole S, Liu W, Soares MB, Bonaldo MF, Hirvasniemi A, de la Chapelle A, Gilliam TC, Lehesjoki AE . The neuronal ceroid lipofuscinoses in human EPMR and mnd mutant mice are associated with mutations in CLN8 . Nat Genet . 23 . 2 . 233–6 . Oct 1999 . 10508524 . 10.1038/13868 . 23920094 .
2. Web site: Entrez Gene: CLN8 ceroid-lipofuscinosis, neuronal 8 (epilepsy, progressive with mental retardation).
3. di Ronza A, Bajaj L, Sharma J, Sanagasetti D, Lotfi P, Adamski CJ, Collette J, Palmieri M, Amawi A, Popp L, Chang KT, Meschini MC, Leung HE, Segatori L, Simonati A, Sifers RN, Santorelli FM, Sardiello M . 2018 . CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis . Nature Cell Biology . 20. 12. 1370–1377. 10.1038/s41556-018-0228-7. 30397314 . 6277210.
4. di Ronza A, Bajaj L, Sharma J, Sanagasetti D, Lotfi P, Adamski CJ, Collette J, Palmieri M, Amawi A, Popp L, Chang KT, Meschini MC, Leung HE, Segatori L, Simonati A, Sifers RN, Santorelli FM, Sardiello M . 2018 . CLN8 is an endoplasmic reticulum cargo receptor that regulates lysosome biogenesis . Nature Cell Biology . 20. 12. 1370–1377. 10.1038/s41556-018-0228-7. 30397314 . 6277210.
5. Bajaj L, Sharma J, di Ronza A, Zhang P, Eblimit A, Pal R, Roman D, Collette JR, Booth C, Chang KT, Sifers RN, Jung SY, Weimer JM, Chen R, Schekman RW, Sardiello M . A CLN6-CLN8 complex recruits lysosomal enzymes at the ER for Golgi transfer . J Clin Invest . 130. 8. 4118–4132. Jun 2020 . 32597833 . 10.1172/JCI130955 . 7410054 . free .