Expression and localization of Cayman ataxia-related protein, Caytaxin, is regulated in a developmental- and spatial-dependent manner

Brain Res. 2007 Jan 19;1129(1):100-9. doi: 10.1016/j.brainres.2006.10.068. Epub 2006 Dec 8.

Abstract

Mutation of the gene encoding Caytaxin causes human Cayman ataxia by interfering with normal splicing and, in mutant rodents, by reducing normal transcription, which leads to ataxia, dystonia, and mental retardation: These observations suggest that Caytaxin may be crucial for higher brain functions such as motor learning. We generated antibodies against mouse Caytaxin. Interestingly, we found that the expression of Caytaxin is regulated during brain development while quantitative real time RT-PCR indicated that the mRNA level did not change between postnatal days 7 (P7) and P14 in the cerebellum and hippocampus, implying that the expression of Caytaxin may be controlled by a post-transcriptional mechanism. Immunostaining analyses demonstrated that Caytaxin was localized in many brain areas including the cerebellum and hippocampus. Furthermore, Caytaxin was localized to the presynaptic cytosol by the subcellular fractionation of mouse brain and an observation that was confirmed by co-localization studies with synapsin I and VGLUT1. The above data, disease phenotypes, and mutant animals suggest that Caytaxin may be essential for synaptic function. Thus, identifying the role of Caytaxin in synapse maturation may lead to the development of therapeutic interventions for cerebellar ataxia as well as mental disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs / physiology
  • Animals
  • Brain / anatomy & histology
  • Brain / growth & development
  • Brain / metabolism*
  • Cell Line
  • Cells, Cultured
  • Cerebellar Ataxia / genetics
  • Cerebellar Ataxia / metabolism
  • Cerebellar Ataxia / physiopathology
  • Cerebellum / anatomy & histology
  • Cerebellum / growth & development
  • Cerebellum / metabolism
  • Cytosol / metabolism
  • Cytosol / ultrastructure
  • Genetic Predisposition to Disease / genetics
  • Hippocampus / anatomy & histology
  • Hippocampus / growth & development
  • Hippocampus / metabolism*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • Presynaptic Terminals / metabolism
  • Presynaptic Terminals / ultrastructure
  • RNA, Messenger
  • Rats
  • Rats, Wistar
  • Sequence Homology, Amino Acid
  • Subcellular Fractions
  • Synapsins / metabolism
  • Vesicular Glutamate Transport Protein 1 / metabolism

Substances

  • Atcay protein, mouse
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Slc17a7 protein, mouse
  • Synapsins
  • Vesicular Glutamate Transport Protein 1
  • atcay protein, rat