Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development

Sangmi Lim, Scott Naisbitt, Jiyoung Yoon, Jong-Ik Hwang, Pann Ghill Suh, Morgan Sheng, Kim Eunjoon

Research output: Contribution to journalArticle

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Abstract

Shank1, Shank2, and Shank3 constitute a family of proteins that may function as molecular scaffolds in the postsynaptic density (PSD). Shank directly interacts with GKAP and Homer, thus potentially bridging the N- methyl-D-aspartate 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., Weinberg, R. J., Worley, 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., Doan, 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/Dlg/ZO-1 domain, a sterile α motif domain, and a proline-rich region. By characterizing Shank cDNA clones and RT-PCR products, we found that there are four sites for alternative splicing in Shank1 and another four sites in Shank2, some of which result in deletion of specific domains of the Shank protein. In addition, 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 marked 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 developing rat brains as early as postnatal day 7. These results suggest that alternative splicing in the Shank family may be a mechanism that regulates the molecular structure of Shank and the spectrum of Shank- interacting proteins in the PSDs of adult and developing brain.

Original languageEnglish
Pages (from-to)29510-29518
Number of pages9
JournalJournal of Biological Chemistry
Volume274
Issue number41
DOIs
Publication statusPublished - 1999 Oct 8
Externally publishedYes

Fingerprint

Alternative Splicing
Brain
Post-Synaptic Density
Genes
Rats
Proteins
Neurons
Ankyrin Repeat
Protein Interaction Domains and Motifs
src Homology Domains
Molecular Structure
N-Methyl-D-Aspartate Receptors
Proline
Scaffolds
Synapses
Molecular structure
Complementary DNA
Clone Cells
Staining and Labeling
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Biochemistry

Cite this

Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development. / Lim, Sangmi; Naisbitt, Scott; Yoon, Jiyoung; Hwang, Jong-Ik; Suh, Pann Ghill; Sheng, Morgan; Eunjoon, Kim.

In: Journal of Biological Chemistry, Vol. 274, No. 41, 08.10.1999, p. 29510-29518.

Research output: Contribution to journalArticle

Lim, Sangmi ; Naisbitt, Scott ; Yoon, Jiyoung ; Hwang, Jong-Ik ; Suh, Pann Ghill ; Sheng, Morgan ; Eunjoon, Kim. / Characterization of the Shank family of synaptic proteins. Multiple genes, alternative splicing, and differential expression in brain and development. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 41. pp. 29510-29518.
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AU - Suh, Pann Ghill

AU - Sheng, Morgan

AU - Eunjoon, Kim

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