S. Lim et al., Characterization of the Shank family of synaptic proteins - Multiple genes, alternative splicing, and differential expression in brain and development, J BIOL CHEM, 274(41), 1999, pp. 29510-29518
Shank1, Shank2, and Shank3 constitute a family of proteins that may functio
n as molecular scaffolds in the postsynaptic density (PSD). Shank directly
interacts with GKAP and Homer, thus potentially bridging the N-methyl-D-asp
artate receptor-PSD-95-GKAP complex and the mGluR-Homer complex in synapses
(Naisbitt, S., Kim, E., Tu, J. C., Xiao, B., Sala, S., Valtschanoff, J., W
einberg, R J., morley, P. F., and Sheng, M. (1999) Neuron 23, 569-582; Tu,
J. C., Xiao, B., Naisbitt, S., Yuan, J. P., Petralia, R. S., Brakeman, P.,
Dean, A., Aakalu, V. K., Lanahan, A. A., Sheng, M., and Worley, P. F. (1999
) Neuron 23, 583-592). Shank contains multiple domains for protein-protein
interaction including ankyrin repeats, an SH3 domain, a PSD-95/DIg/ZO-1 dom
ain, a sterile a motif domain, and a proline-rich region. By characterizing
Shank cDNA clones and RT-PCR products, we found that there are four sites
far alternative splicing in Shank1 and another four sites in Shank2, some o
f which result in deletion of specific domains of the Shank protein. In add
ition, the expression of the splice variants is differentially regulated in
different regions of rat brain during development. Immunoblot analysis of
Shank proteins in rat brain using five different Shank antibodies reveals m
arked heterogeneity in size (120-240 kDa) and differential. spatiotemporal
expression. Shank1 immunoreactivity is concentrated at excitatory synaptic
sites in adult brain, and the punctate staining of Shank1 is seen in develo
ping rat brains as early as postnatal day 7. These results suggest that alt
ernative splicing in the Shank family may be a mechanism that regulates the
molecular structure of Shank and the spectrum of Shank-interacting protein
s in the PSDs of adult and developing brain.