期刊
BRAIN
卷 133, 期 -, 页码 2462-2474出版社
OXFORD UNIV PRESS
DOI: 10.1093/brain/awq168
关键词
SH3TC2 / KIAA1985; Rab11; recycling endosome; Schwann cell myelination; Charcot-Marie-Tooth neuropathy
资金
- RWTH Aachen University
- Interdisciplinary Centre for Clinical Research BIOMAT within the Faculty of Medicine
- Swiss National Science Foundation
- National Centre of Competence in Research
- Neural Plasticity and Repair
- Deutsche Forschungsgemeinschaft
Patients with Charcot-Marie-Tooth neuropathy and gene targeting in mice revealed an essential role for the SH3TC2 gene in peripheral nerve myelination. SH3TC2 expression is restricted to Schwann cells in the peripheral nervous system, and the gene product, SH3TC2, localizes to the perinuclear recycling compartment. Here, we show that SH3TC2 interacts with the small guanosine triphosphatase Rab11, which is known to regulate the recycling of internalized membranes and receptors back to the cell surface. Results of protein binding studies and transferrin receptor trafficking are in line with a role of SH3TC2 as a Rab11 effector molecule. Consistent with a function of Rab11 in Schwann cell myelination, SH3TC2 mutations that cause neuropathy disrupt the SH3TC2/Rab11 interaction, and forced expression of dominant negative Rab11 strongly impairs myelin formation in vitro. Our data indicate that the SH3TC2/Rab11 interaction is relevant for peripheral nerve pathophysiology and place endosomal recycling on the list of cellular mechanisms involved in Schwann cell myelination.
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