LRRK2 kinase modulates glucose-stimulated insulin secretion via RAB8 phosphorylation and ciliogenesis

Cookson MR (2010) The role of leucine-rich repeat kinase 2 (LRRK2) in parkinson’s disease. Nat Rev Neurosci 11:791–797. https://doi.org/10.1038/nrn2935

Article  CAS  PubMed  PubMed Central  Google Scholar 

Monfrini E, Di Fonzo A (2017) Leucine-Rich repeat kinase (LRRK2) genetics and parkinson’s disease. Adv Neurobiol 14:3–30. https://doi.org/10.1007/978-3-319-49969-7_1

Article  PubMed  Google Scholar 

Obeso JA, Stamelou M, Goetz CG et al (2017) Past, present, and future of parkinson’s disease: A special essay on the 200th anniversary of the shaking palsy. Mov Disord 32:1264–1310. https://doi.org/10.1002/mds.27115

Article  CAS  PubMed  PubMed Central  Google Scholar 

Goldwurm S, Di Fonzo A, Simons EJ et al (2005) The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset parkinson’s disease and originates from a common ancestor. J Med Genet 42:e65. https://doi.org/10.1136/jmg.2005.035568

Article  CAS  PubMed  PubMed Central  Google Scholar 

Greggio E, Jain S, Kingsbury A et al (2006) Kinase activity is required for the toxic effects of mutant LRRK2/dardarin. Neurobiol Dis 23:329–341. https://doi.org/10.1016/j.nbd.2006.04.001

Article  CAS  PubMed  Google Scholar 

Steger M, Tonelli F, Ito G et al (2016) Phosphoproteomics reveals that parkinson’s disease kinase LRRK2 regulates a subset of Rab GTPases. eLife 5:e12813. https://doi.org/10.7554/eLife.12813

Article  PubMed  PubMed Central  Google Scholar 

Tsafaras G, Baekelandt V (2022) The role of LRRK2 in the periphery: link with parkinson’s disease and inflammatory diseases. Neurobiol Dis 172:105806. https://doi.org/10.1016/j.nbd.2022.105806

Article  CAS  PubMed  Google Scholar 

Funk N, Munz M, Ott T et al (2019) The parkinson’s disease-linked Leucine-rich repeat kinase 2 (LRRK2) is required for insulin-stimulated translocation of GLUT4. Sci Rep 9:4515. https://doi.org/10.1038/s41598-019-40808-y

Article  CAS  PubMed  PubMed Central  Google Scholar 

Imai M, Kawakami F, Kubo M et al (2020) LRRK2 Inhibition ameliorates Dexamethasone-Induced glucose intolerance via prevents impairment in GLUT4 membrane translocation in adipocytes. Biol Pharm Bull 43:1660–1668. https://doi.org/10.1248/bpb.b20-00377

Article  CAS  PubMed  Google Scholar 

Kawakami F, Imai M, Isaka Y et al (2023) LRRK2 negatively regulates glucose tolerance via regulation of membrane translocation of GLUT4 in adipocytes. FEBS Open Bio 13:2200–2214. https://doi.org/10.1002/2211-5463.13717

Article  CAS  PubMed  PubMed Central  Google Scholar 

Paisán-Ruíz C, Jain S, Evans EW et al (2004) Cloning of the gene containing mutations that cause PARK8-linked parkinson’s disease. Neuron 44:595–600. https://doi.org/10.1016/j.neuron.2004.10.023

Article  PubMed  Google Scholar 

Athauda D, Foltynie T (2016) Insulin resistance and parkinson’s disease: A new target for disease modification? Prog Neurobiol 145–146:98–120. https://doi.org/10.1016/j.pneurobio.2016.10.001

Article  CAS  PubMed  Google Scholar 

Healy DG, Falchi M, O’Sullivan SS et al (2008) Phenotype, genotype, and worldwide genetic penetrance of LRRK2-associated parkinson’s disease: a case-control study. Lancet Neurol 7:583–590. https://doi.org/10.1016/S1474-4422(08)70117-0

Article  CAS  PubMed  PubMed Central  Google Scholar 

Di Cairano ES, Moretti S, Marciani P et al (2016) Neurotransmitters and neuropeptides: new players in the control of islet of langerhans’ cell mass and function. J Cell Physiol 231:756–767. https://doi.org/10.1002/jcp.25176

Article  CAS  PubMed  Google Scholar 

Wheeler MB, Sheu L, Ghai M et al (1996) Characterization of SNARE protein expression in beta cell lines and pancreatic Islets. Endocrinology 137:1340–1348. https://doi.org/10.1210/endo.137.4.8625909

Article  CAS  PubMed  Google Scholar 

Regazzi R, Ravazzola M, Iezzi M et al (1996) Expression, localization and functional role of small GTPases of the Rab3 family in insulin-secreting cells. J Cell Sci 109(Pt 9):2265–2273

CAS  PubMed  Google Scholar 

Galli A, Arunagiri A, Dule N et al (2023) Cholesterol redistribution in pancreatic β-Cells: A flexible path to regulate insulin secretion. Biomolecules 13:224. https://doi.org/10.3390/biom13020224

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sanchez GM, Incedal TC, Prada J et al (2023) The β-cell primary cilium is an autonomous Ca2 + compartment for paracrine GABA signaling. J Cell Biol 222:e202108101. https://doi.org/10.1083/jcb.202108101

Article  CAS  PubMed  Google Scholar 

Cho JH, Li ZA, Zhu L et al (2022) Islet primary cilia motility controls insulin secretion. Sci Adv 8:eabq8486. https://doi.org/10.1126/sciadv.abq8486

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pablos M, Casanueva-Álvarez E, González-Casimiro CM et al (2022) Primary cilia in pancreatic β- and α-Cells: time to revisit the role of Insulin-Degrading enzyme. Front Endocrinol (Lausanne) 13:922825. https://doi.org/10.3389/fendo.2022.922825

Article  PubMed  Google Scholar 

Piccoli G, Volta M (2021) LRRK2 along the golgi and lysosome connection: a jamming situation. Biochem Soc Trans 49:2063–2072. https://doi.org/10.1042/BST20201146

Article  CAS  PubMed  PubMed Central  Google Scholar 

Boecker CA (2023) The role of LRRK2 in intracellular organelle dynamics. J Mol Biol 435:167998. https://doi.org/10.1016/j.jmb.2023.167998

Article  CAS  PubMed  Google Scholar 

Dhekne HS, Yanatori I, Gomez RC et al (2018) A pathway for parkinson’s disease LRRK2 kinase to block primary cilia and Sonic Hedgehog signaling in the brain. Elife 7:e40202. https://doi.org/10.7554/eLife.40202

Article  PubMed  PubMed Central  Google Scholar 

Babbey CM, Bacallao RL, Dunn KW (2010) Rab10 associates with primary cilia and the exocyst complex in renal epithelial cells. Am J Physiol Ren Physiol 299:F495–506. https://doi.org/10.1152/ajprenal.00198.2010

Article  CAS  Google Scholar 

Blacque OE, Scheidel N, Kuhns S (2018) Rab GTPases in cilium formation and function. Small GTPases 9:76–94. https://doi.org/10.1080/21541248.2017.1353847

Article  CAS  PubMed  Google Scholar 

Ishikawa H, Marshall WF (2011) Ciliogenesis: Building the cell’s antenna. Nat Rev Mol Cell Biol 12:222–234. https://doi.org/10.1038/nrm3085

Article  CAS  PubMed  Google Scholar 

Dhekne HS, Tonelli F, Yeshaw WM et al (2023) Genome-wide screen reveals Rab12 GTPase as a critical activator of parkinson’s disease-linked LRRK2 kinase. Elife 12:e87098. https://doi.org/10.7554/eLife.87098

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bedford C, Sears C, Perez-Carrion M et al (2016) LRRK2 regulates Voltage-Gated calcium channel function. Front Mol Neurosci 9:35. https://doi.org/10.3389/fnmol.2016.00035

Article  CAS  PubMed 

Comments (0)

No login
gif