KIAA1985, a Protein Mutant in Charcot-Marie-Tooth Neuropathy, Links Peripheral Nerve Myelination to Endosomal Recycling Pathways
Details
Serval ID
serval:BIB_FFF343101B16
Type
Inproceedings: an article in a conference proceedings.
Publication sub-type
Abstract (Abstract): shot summary in a article that contain essentials elements presented during a scientific conference, lecture or from a poster.
Collection
Publications
Institution
Title
KIAA1985, a Protein Mutant in Charcot-Marie-Tooth Neuropathy, Links Peripheral Nerve Myelination to Endosomal Recycling Pathways
Title of the conference
9th European Meeting on Glial Cells in Health and Disease
Address
Paris, France, September 08-12, 2009
ISBN
0894-1491
Publication state
Published
Issued date
2009
Peer-reviewed
Oui
Volume
57
Series
Glia
Pages
95
Language
english
Notes
Meeting Abstract
Abstract
Charcot-Marie-Tooth neuropathy (CMT) represents a heterogenous group of inherited disorders of the peripheral nervous system. One form of autosomal recessive demyelinating CMT (CMT4C, 5q32) is caused by mutations in the gene encoding KIAA1985, a protein of so far unknown function. Here we show that KIAA1985 is exclusively expressed in Schwann cells. KIAA1985 is tethered to cellular membranes through an N-terminal myristic acid anchor and localizes to the perinuclear recycling compartment. A search for proteins that interact with KIAA1985 identified the small GTPase Rab11, a key regulator of recycling endosome functions. CMT4C-related missense mutations disrupt the KIAA1985/Rab11 interaction. Protein binding studies indicate that KIAA1985 functions as a Rab11 effector, as it interacts only with active forms of Rab11 (WT and Q70L) and does not interact with the GDP locked mutant (S25N). Consistent with a function of Rab11 in Schwann cell myelination, myelin formation was strongly impaired when dorsal root ganglion neurons were co-cultured with Schwann cells infected with Rab11 S25N. Our data indicate that the KIAA1985/Rab11 interaction is relevant for peripheral nerve pathophysiology and place endosomal recycling on the list of cellular mechanisms involved in Schwann cell myelination.
Web of science
Create date
04/12/2009 10:02
Last modification date
20/08/2019 17:30