Synaptic Transmission

Control of neurotransmitter release by an internal gel matrix in synaptic vesicles. Reigada, D. et al. Proc. Natl Acad. Sci. USA 100, 3485–3490 (2003)

In neurotransmitter vesicles from Torpedo, 95% of acetylcholine and ATP is found to be adsorbed to an intravesicular proteoglycan matrix, rather than being in free solution. This 'smart gel', which includes the proteoglycan SV2, releases neurotransmitter in response to changes in ion concentration, and could modulate the amount of transmitter released during vesicle fusion.

Neurodegeneration

Parkin suppresses dopaminergic neuron-selective neurotoxicity induced by Pael-R in Drosophila. Yang, Y. et al. Neuron 37, 911–924 (2003)

Mutations in the parkin gene that abolish the protein's E3 ubiquitin ligase activity are associated with early-onset Parkinson's disease. One substrate of Parkin is Pael-R, and Yang et al. show that expression of human PAELR in Drosophila causes degeneration of dopamine neurons, and that co-expression of Parkin prevents this degeneration.

Cell Biology Of The Neuron

The role of presenilin cofactors in the γ-secretase complex. Takasugi, N. et al. Nature 422, 438–441 (2003)

Reconstitution of γ-secretase activity. Edbauer, D. Nature Cell Biol. 7 April 2003 (10.1038/ncb960)

These two papers provide new insights into the components of γ-secretase, an unusual protease that is involved in the formation of amyloid-β peptide by cleavage of amyloid precursor protein. Edbauer et al. show that γ-secretase activity can be reconstituted in yeast by the co-expression of human presenilin and three putative cofactors — nicastrin, APH1 and PEN2. Takasugi et al., meanwhile, have found evidence that, in Drosophila, APH1 stabilises the presenilin holoprotein in the complex formed by the proteins. PEN2 then seems to interact with the APH1–presenilin–nicastrin complex to cause endoproteolysis of presenilin and confer γ-secretase activity on the complex.

Development

Wnt-mediated axon guidance via the Drosophila Derailed receptor. Yoshikawa, S. et al. Nature 16 March 2003 (10.1038/nature01522)

In Drosophila, axons that cross the midline during development through the anterior commissure express an atypical tyrosine kinase receptor, Derailed, that prevents them from entering the posterior commissure. Yoshikawa et al. show that Derailed mediates this repulsion by acting as a receptor for Wnt5, a secreted signalling molecule, and that Wnt5 is expressed by neurons around the posterior commissure.