Mutations in the Small GTP-ase Late Endosomal Protein RAB7 Cause Charcot-Marie-Tooth Type 2B Neuropathy

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 2003 Jan 25

PMID 12545426

Citations 197

Authors

Kristien Verhoeven

Peter De Jonghe

Katrien Coen

Nathalie Verpoorten

Michaela Auer-Grumbach

Jennifer M Kwon

David Fitzpatrick

Eric Schmedding

Els De Vriendt

An Jacobs

Veerle Van Gerwen

Klaus Wagner

Hans-Peter Hartung

Vincent Timmerman

Affiliations

Soon will be listed here.

Abstract

Charcot-Marie-Tooth type 2B (CMT2B) is clinically characterized by marked distal muscle weakness and wasting and a high frequency of foot ulcers, infections, and amputations of the toes because of recurrent infections. CMT2B maps to chromosome 3q13-q22. We refined the CMT2B locus to a 2.5-cM region and report two missense mutations (Leu129Phe and Val162Met) in the small GTP-ase late endosomal protein RAB7 which causes the CMT2B phenotype in three extended families and in three patients with a positive family history. The alignment of RAB7 orthologs shows that both missense mutations target highly conserved amino acid residues. RAB7 is ubiquitously expressed, and we found expression in sensory and motor neurons.

Citing Articles

A novel missense mutation causes autosomal dominant Charcot-Marie-Tooth disease type 4B3.

Liu H, Dong J, Xie Z, Yu L Front Neurol. 2024; 15:1495711.

PMID: 39664754 PMC: 11633322. DOI: 10.3389/fneur.2024.1495711.

tsCRISPR based identification of Rab proteins required for the recycling of TRPL ion channel.

Zeger M, Stanislawczyk L, Bulic M, Binder A, Huber A Front Cell Dev Biol. 2024; 12:1444953.

PMID: 39372952 PMC: 11450138. DOI: 10.3389/fcell.2024.1444953.

Defects of mitochondria-lysosomes communication induce secretion of mitochondria-derived vesicles and drive chemoresistance in ovarian cancer cells.

Gagliardi S, Mitruccio M, Di Corato R, Romano R, Aloisi A, Rinaldi R Cell Commun Signal. 2024; 22(1):165.

PMID: 38448982 PMC: 10916030. DOI: 10.1186/s12964-024-01507-y.

Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy.

Guo Y, Xiang P, Sun X, Liu W, Zhou J, Yin B Signal Transduct Target Ther. 2024; 9(1):32.

PMID: 38351062 PMC: 10864363. DOI: 10.1038/s41392-024-01742-2.

Neuronal Autophagy: Regulations and Implications in Health and Disease.

Lienard C, Pintart A, Bomont P Cells. 2024; 13(1).

PMID: 38201307 PMC: 10778363. DOI: 10.3390/cells13010103.

References

Nielsen E, Severin F, Backer J, Hyman A, Zerial M . Rab5 regulates motility of early endosomes on microtubules. Nat Cell Biol. 1999; 1(6):376-82. DOI: 10.1038/14075. View

Press B, Feng Y, Hoflack B, Wandinger-Ness A . Mutant Rab7 causes the accumulation of cathepsin D and cation-independent mannose 6-phosphate receptor in an early endocytic compartment. J Cell Biol. 1998; 140(5):1075-89. PMC: 2132709. DOI: 10.1083/jcb.140.5.1075. View

Auer-Grumbach M, De Jonghe P, Wagner K, Verhoeven K, Hartung H, Timmerman V . Phenotype-genotype correlations in a CMT2B family with refined 3q13-q22 locus. Neurology. 2000; 55(10):1552-7. DOI: 10.1212/wnl.55.10.1552. View

Cantalupo G, Alifano P, Roberti V, Bruni C, Bucci C . Rab-interacting lysosomal protein (RILP): the Rab7 effector required for transport to lysosomes. EMBO J. 2001; 20(4):683-93. PMC: 145419. DOI: 10.1093/emboj/20.4.683. View

Bejaoui K, Wu C, Scheffler M, Haan G, Ashby P, Wu L . SPTLC1 is mutated in hereditary sensory neuropathy, type 1. Nat Genet. 2001; 27(3):261-2. DOI: 10.1038/85817. View

Dawkins J, Hulme D, Brahmbhatt S, Auer-Grumbach M, Nicholson G . Mutations in SPTLC1, encoding serine palmitoyltransferase, long chain base subunit-1, cause hereditary sensory neuropathy type I. Nat Genet. 2001; 27(3):309-12. DOI: 10.1038/85879. View

Eggenschwiler J, Espinoza E, Anderson K . Rab23 is an essential negative regulator of the mouse Sonic hedgehog signalling pathway. Nature. 2001; 412(6843):194-8. DOI: 10.1038/35084089. View

Jordens I, Fernandez-Borja M, Marsman M, Dusseljee S, Janssen L, Calafat J . The Rab7 effector protein RILP controls lysosomal transport by inducing the recruitment of dynein-dynactin motors. Curr Biol. 2001; 11(21):1680-5. DOI: 10.1016/s0960-9822(01)00531-0. View

Tang B . Protein trafficking mechanisms associated with neurite outgrowth and polarized sorting in neurons. J Neurochem. 2001; 79(5):923-30. DOI: 10.1046/j.1471-4159.2001.00674.x. View

10.

Seabra M, Mules E, Hume A . Rab GTPases, intracellular traffic and disease. Trends Mol Med. 2002; 8(1):23-30. DOI: 10.1016/s1471-4914(01)02227-4. View

11.

Bellone E, Rodolico C, Toscano A, Di Maria E, Cassandrini D, Pizzuti A . A family with autosomal dominant mutilating neuropathy not linked to either Charcot-Marie-Tooth disease type 2B (CMT2B) or hereditary sensory neuropathy type I (HSN I) loci. Neuromuscul Disord. 2002; 12(3):286-91. DOI: 10.1016/s0960-8966(01)00282-6. View

12.

Lebrand C, Corti M, Goodson H, Cosson P, Cavalli V, Mayran N . Late endosome motility depends on lipids via the small GTPase Rab7. EMBO J. 2002; 21(6):1289-300. PMC: 125356. DOI: 10.1093/emboj/21.6.1289. View

13.

Choudhury A, Dominguez M, Puri V, Sharma D, Narita K, Wheatley C . Rab proteins mediate Golgi transport of caveola-internalized glycosphingolipids and correct lipid trafficking in Niemann-Pick C cells. J Clin Invest. 2002; 109(12):1541-50. PMC: 151017. DOI: 10.1172/JCI15420. View

14.

Auer-Grumbach M, De Jonghe P, Verhoeven K, Timmerman V, Wagner K, Hartung H . Autosomal dominant inherited neuropathies with prominent sensory loss and mutilations: a review. Arch Neurol. 2003; 60(3):329-34. DOI: 10.1001/archneur.60.3.329. View

15.

Kwon J, ELLIOTT J, Yee W, Ivanovich J, Scavarda N, Moolsintong P . Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q. Am J Hum Genet. 1995; 57(4):853-8. PMC: 1801519. View

16.

Vitelli R, Chiariello M, Lattero D, Bruni C, Bucci C . Molecular cloning and expression analysis of the human Rab7 GTP-ase complementary deoxyribonucleic acid. Biochem Biophys Res Commun. 1996; 229(3):887-90. DOI: 10.1006/bbrc.1996.1897. View

17.

Geppert M, Goda Y, Stevens C, Sudhof T . The small GTP-binding protein Rab3A regulates a late step in synaptic vesicle fusion. Nature. 1997; 387(6635):810-4. DOI: 10.1038/42954. View

18.

De Jonghe P, Timmerman V, Fitzpatrick D, Spoelders P, Martin J, Van Broeckhoven C . Mutilating neuropathic ulcerations in a chromosome 3q13-q22 linked Charcot-Marie-Tooth disease type 2B family. J Neurol Neurosurg Psychiatry. 1997; 62(6):570-3. PMC: 1074138. DOI: 10.1136/jnnp.62.6.570. View

19.

Echard A, Jollivet F, Martinez O, Lacapere J, Rousselet A, Janoueix-Lerosey I . Interaction of a Golgi-associated kinesin-like protein with Rab6. Science. 1998; 279(5350):580-5. DOI: 10.1126/science.279.5350.580. View

20.

Auer-Grumbach M, Wagner K, Timmerman V, De Jonghe P, Hartung H . Ulcero-mutilating neuropathy in an Austrian kinship without linkage to hereditary motor and sensory neuropathy IIB and hereditary sensory neuropathy I loci. Neurology. 2000; 54(1):45-52. DOI: 10.1212/wnl.54.1.45. View