PDZ-containing proteins: alternative splicing as a source of functional diversity

Brain Res Brain Res Rev. 2004 Dec;47(1-3):105-15. doi: 10.1016/j.brainresrev.2004.06.002.

Abstract

Scaffold proteins allow specific protein complexes to be assembled in particular regions of the cell at which they organize subcellular structures and signal transduction complexes. This characteristic is especially important for neurons, which are highly polarized cells. Among the domains contained by scaffold proteins, the PSD-95, Discs-large, ZO-1 (PDZ) domains are of particular relevance in signal transduction processes and maintenance of neuronal and epithelial polarity. These domains are specialized in the binding of the carboxyl termini of proteins allowing membrane proteins to be localized by the anchoring to the cytoskeleton mediated by PDZ-containing scaffold proteins. In vivo studies carried out in Drosophila have taught that the role of many scaffold proteins is not limited to a single process; thus, in many cases the same genes are expressed in different tissues and participate in apparently very diverse processes. In addition to the differential expression of interactors of scaffold proteins, the expression of variants of these molecular scaffolds as the result of the alternative processing of the genes that encode them is proving to be a very important source of variability and complexity on a main theme. Alternative splicing in the nervous system is well documented, where specific isoforms play roles in neurotransmission, ion channel function, neuronal cell recognition, and are developmentally regulated making it a major mechanism of functional diversity. Here we review the current state of knowledge about the diversity and the known function of PDZ-containing proteins in Drosophila with emphasis in the role played by alternatively processed forms in the diversity of functions attributed to this family of proteins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing / genetics
  • Alternative Splicing / physiology*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cytoskeleton / genetics
  • Cytoskeleton / metabolism*
  • Drosophila melanogaster
  • Gene Expression Regulation / genetics
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Nervous System / metabolism*
  • Nervous System / ultrastructure
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Structure, Tertiary / genetics
  • Protein Structure, Tertiary / physiology
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Carrier Proteins
  • Membrane Proteins
  • Protein Isoforms