Contrasting Localizations of MALS/LIN-7 PDZ Proteins in Brain and Molecular Compensation in Knockout Mice

Hidemi Misawa, Yoshimi Kawasaki, Jack Mellor, Neal Sweeney, Kiwon Jo, Roger A. Nicoll, David S. Bredt

研究成果: Article

43 引用 (Scopus)

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Proteins containing PDZ (postsynaptic density-95, discs large, zonula occludens) domains play a general role in recruiting receptors and enzymes to specific synaptic sites. In Caenorhabditis elegans, a complex of three PDZ proteins, LIN-2/7/10, mediates basolateral targeting of a receptor tyrosine kinase. Homologs of these LIN proteins have also been identified in higher organisms, and here we analyze the MALS/Veli (mammalian LIN-7/vertebrate homolog of LIN-7) proteins in brain. Immunohistochemical staining and in situ hybridization show that MALS occur differentially in discrete populations of neurons throughout the brain. Most neurons express only one MALS protein, although some cells contain two or even all three MALS isoforms. At the subcellular level, MALS proteins are found in both dendritic and axonal locations, suggesting that they may regulate processes at both pre- and postsynaptic sites. Targeted disruption of MALS-1 and MALS-2 does not yield a detectable phenotype, and hippocampal synaptic function and plasticity are intact in the MALS-1/2 double knockouts. Interestingly, MALS-3 protein is dramatically induced in the MALS-1/2 double knockouts, implying that dynamic changes in protein expression may play an important regulatory role for this family of synaptic PDZ proteins.

元の言語English
ページ(範囲)9264-9272
ページ数9
ジャーナルJournal of Biological Chemistry
276
発行部数12
DOI
出版物ステータスPublished - 2001 3 23
外部発表Yes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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