Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 1 June 2004
Vol. 2004, Issue 235, p. tw197
[DOI: 10.1126/scisignal.2352004tw197]

EDITORS' CHOICE

SYNAPTIC FUNCTION Atypical Protein Kinase C: Linking Microtubules and Memory?

Atypical protein kinase C (aPKC), which has been implicated in synaptic plasticity and in memory, occurs in a complex with the PDZ-domain proteins Par-3 (known as Bazooka in Drosophila) and Par-6. This complex is necessary for development of polarity in several systems. Noting that synapses are polarized, Ruiz-Canada et al. investigated the role of aPKC in the development of the Drosophila neuromuscular junction (NMJ). Flies expressing loss-of-function dapkc mutants had fewer synaptic boutons, as did flies expressing constitutively active aPKC either pre- or postsynaptically. Immunocytochemical analysis revealed that aPKC was associated with pre- and postsynaptic microtubules. In flies with reduced aPKC activity, presynaptic microtubules were fragmented, whereas constitutively active presynaptic aPKC promoted microtubule stability, an effect that depended on the protein Futsch (which protects microtubules from depolymerization). Moreover, constitutively active presynaptic aPKC enhanced Futsch association with microtubules. Postsynaptically, decreased aPKC activity led to a reduction in the peribouton actin-rich cytoskeleton and expansion of the microtubule network, whereas increased aPKC activity had the opposite effects. Both gain- and loss-of-function mutants were associated with decreases in miniature excitatory junction potential (mEJP) frequency and in quantal content (presynaptic effects); however, effects on mEJP amplitude (which are generally postsynaptic) differed. Decreased aPKC activity was associated with increased mEJP amplitude and more intense glutamate receptor immunoreactivity, whereas postsynaptic overexpression was associated with decreased mEJP amplitude and altered receptor distribution. Par-3 and Par-6 were also found pre- and postsynaptically, and their mutation decreased bouton formation. Thus, aPKC affects organization of the synaptic cytoskeleton, altering NMJ development and synaptic efficacy, leading the authors to suggest that its effects on synaptic plasticity and memory may involve regulation of synaptic cytoskeleton organization.

C. Ruiz-Canada, J. Ashley, S. Moeckel-Cole, E. Drier, J. Yin, V. Budnik, New synaptic bouton formation is disrupted by misregulation of microtubule stability in aPKC mutants. Neuron 42, 567-580 (2004). [Online Journal]

Citation: Atypical Protein Kinase C: Linking Microtubules and Memory? Sci. STKE 2004, tw197 (2004).



To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882