Analyses of the spatiotemporal expression and subcellular localization of liprin-α proteins

J Comp Neurol. 2011 Oct 15;519(15):3019-39. doi: 10.1002/cne.22664.

Abstract

The members of the Liprin-α protein family, Liprin-α1-4, are scaffolding proteins that play important roles in the regulation of synapse assembly and maturation, vesicular trafficking, and cell motility. Recent evidence suggests that despite their high degree of homology, the four isoforms can be differentially regulated and fulfill diverging functions. However, to date their precise regional and subcellular distribution has remained elusive. Here, we examine the spatiotemporal expression patterns of Liprins-α in the rodent by using in situ hybridization, immunoblotting, and immunochemistry of primary cells as well as brain and retina sections. We show that Liprin-α1-4 mRNA and protein are widely expressed throughout the developing and adult central nervous system, with Liprin-α2 and -α3 being the major Liprin-α isoforms in the brain. Our data show that the four Liprin-α proteins differ in their regional distribution, in particular in the hippocampus, the cerebellum, and the olfactory bulb. Liprin-α1 exhibits a unique spatiotemporal expression pattern as its levels decrease during synaptogenesis, and it is the only Liprin-α with substantial non-neuronal expression. Immunocytochemistry of cultured primary neurons with pre- and postsynaptic marker proteins shows all four Liprins-α to be present at synapses and nonsynaptic sites to varying degrees. Together, these results show that neurons in different brain regions express a distinct complement of Liprin-α proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Brain / embryology
  • Brain / growth & development
  • Brain / metabolism
  • Cells, Cultured
  • Disks Large Homolog 4 Protein
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation, Developmental*
  • Guanylate Kinases / metabolism
  • HEK293 Cells
  • Hippocampus / cytology
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Proteins / genetics
  • Proteins / metabolism*
  • Rats
  • Rats, Wistar
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Tissue Distribution

Substances

  • Adaptor Proteins, Signal Transducing
  • Bsn protein, mouse
  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Ppfia1 protein, mouse
  • Ppfia1 protein, rat
  • Protein Isoforms
  • Proteins
  • Recombinant Fusion Proteins
  • Rims1 protein, mouse
  • Guanylate Kinases
  • GTP-Binding Proteins