Claudin 11 stops the leaks

Devaux and Gow demonstrate how a tight junction protein called claudin 11 makes the neuronal myelin sheath a snug fi t. Like the rubber coating on a copper wire, the myelin sheath—a membrane extension of glial cells that spirals around the axons of neurons—creates an insulation layer that prevents current leakage from axons and aids electrical conduction along the length of the axon. Claudin 11 forms tight junctions between successive spiral layers of the myelin sheath, but it was unknown whether it was required for myelin to act as a good insulator. To examine this question, Devaux and Gow compared electrical recordings from the optic nerve of wild-type and claudin 11 knockout mice. They found that although claudin 11 defi ciency caused no gross defects in the appearance of the myelin sheath, it slowed electrical signals—at least in neurons with small-diameter axons. Using a computer model that incorporates the resistive and capacitive properties of axons (and their myelin sheaths), the authors showed that claudin 11 adds to the electrical resistance of myelin by preventing leakage of charged ions (and electrical current) through the spiral space between myelin layers. The reduced resistance in the absence of claudin 11 affects small-diameter axons most severely because such axons have thinner myelin sheaths and thus less insulation to begin with. Because neurons with small-diameter axons are mostly found in the CNS, the authors speculate that defects in claudin 11 could be associated with defi cits in cognition and perception, like those found in schizophrenia or neurodegenerative diseases. A study by Narendra et al. suggests that Parkin, the product of the Parkinson's disease-related gene Park2, prompts neuronal survival by clearing the cell of its damaged mitochondria. Loss-of-function mutations in the gene Park2, which encodes an E3 ubiquitin ligase (Parkin), are implicated in half the cases of recessive familial early-onset Parkinson's disease. Several lines of evidence suggest that Parkin loss is associated with mitochondrial dysfunction, but exactly how was unknown. To learn more about Parkin's role in cells, Narendra et al. examined the protein's subcellular location. They found that Parkin was present in the cytoplasm of most cells, but translocated to mitochondria in cells that had undergone mitochondrial damage such as membrane depolarization. Damaged mitochondria can trigger cell death pathways; indeed, dysregulation of mitochondrial health was already thought to be a possible cause of the neuronal cell death associated with Parkinson's disease. The relocation of Parkin …