GDAP1, the protein causing Charcot–Marie–Tooth disease type 4A, is expressed in neurons and is associated with mitochondria

2005/03/16 by Laia Pedrola, Antonio Espert, Xingyao Wu +3 · 182 citations
Neuroscience · #Hereditary Neurological Disorders #Genetic Neurodegenerative Diseases #Neurological diseases and metabolism #Biology #Mitochondrion #Degenerative disease #Disease #Genetics #Type (biology) #Cell biology #Central nervous system disease #Neuroscience #Internal medicine

paper · pdf · doi:10.1093/hmg/ddi121

published in Human Molecular Genetics 14(8), 1087-1094 (Oxford University Press)

openalex publication_date 2005/03/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29

Abstract

Mutations in GDAP1, the ganglioside-induced differentiation-associated protein 1 gene, cause Charcot-Marie-Tooth (CMT) type 4A, a severe autosomal recessive form of neuropathy associated with either demyelinating or axonal phenotypes. Here, we demonstrate that GDAP1 has far greater expression in neurons than in myelinating Schwann cells. We investigated cell localization of GDAP1 in a human neuroblastoma cell line by means of transient overexpression and co-localization with organelle markers in COS-7 cells and by western blot analysis of subcell fractions with anti-GDAP1 polyclonal antibodies. We observed that GDAP1 is localized in mitochondria. We also show that C-terminal transmembrane domains are necessary for the correct localization in mitochondria; however, missense mutations do not change the mitochondrial pattern of the wild-type protein. Our findings suggest that CMT4A disease is in fact a mitochondrial neuropathy mainly involving axons and represents a disease belonging to the new category of mitochondrial disorders caused by mutations in nuclear genes. We postulate that GDAP1 may be related to the maintenance of the mitochondrial network.

Citations

• Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A
• Isolation of 10 Differentially Expressed cDNAs in Differentiated Neuro2a Cells Induced Through Controlled Expression of the GD3 Synthase Gene
• Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes.
• Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21
• The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease
• Genetic and clinical aspects of Charcot‐Marie‐Tooth's disease
• Identification of novel GDAP1 mutations causing autosomal recessive Charcot-Marie-Tooth disease
• Evolutionary and Structural Analyses of GDAP1, Involved in Charcot-Marie-Tooth Disease, Characterize a Novel Class of Glutathione Transferase-Related Genes
• CMT4A: Identification of a Hispanic GDAP1 founder mutation
• Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy

Cited by

• GDAP1 [wikipedia]