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Calcium channels SMA

Calcium channels (red) cluster at presynaptic termini, but not without SMN (right).

A paralyzing disease might best be treated by exciting motoneurons rather than saving them, report Jablonka et al.

The paralysis that occurs in patients with spinal muscular atrophy (SMA) stems from defective SMN1, a protein that interacts with mRNA transport factors. Motoneurons seem to be particularly sensitive to the transport problems, perhaps due to their considerable length. In mice with mutant SMN1, ß-actin mRNA is not brought correctly to axonal tips, where it normally forms scaffolds needed for vesicle trafficking to the presynaptic membrane.

The scarcity of ß-actin scaffolds, the team now shows, severely hinders the delivery of calcium channels to the membrane. Without the usual dense clusters of these channels, calcium influx and thus neuronal excitation were impaired. The excitation defects could be reversed by stimulating the production of SMN protein from a relative of the SMN1 gene, called SMN2.

Although motoneurons die off in SMA, previous analysis of a mouse model indicated that the disease manifested before this death. The findings from Jablonka et al. confirm that it's not motoneuron death that's to blame and suggest instead that the problem is a lack of motoneuron function. Restoring presynaptic calcium channel clustering and neuronal firing might be a promising therapeutic avenue.

Reference:

Jablonka, S., et al. 2007. J. Cell Biol. 179:139–149.[Abstract/Free Full Text]

Ruth Williams

ruth.williams{at}rockefeller.edu

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Related Article

Defective Ca²⁺ channel clustering in axon terminals disturbs excitability in motoneurons in spinal muscular atrophy

Sibylle Jablonka, Marcus Beck, Barbara Dorothea Lechner, Christine Mayer, and Michael Sendtner
J. Cell Biol. 2007 179: 139-149. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 846K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Williams, R. Search for Related Content PubMed Articles by Williams, R. Related Collections Related Article Social Bookmarking                            What's this?