Identification of a novel human MT5-MMP transcript variant in multipotent NT2 cells

Heather H Ross1, Helen L Fillmore

  • 1Department of Anatomy and Neurobiology, Virginia Commonwealth University Medical Center, Richmond, VA, United States.

FEBS Letters
|December 8, 2007
PubMed

Insights

Researchers discovered a new variant of membrane-type 5 matrix metalloproteinase (MT5-MMP) in the human brain. This novel MT5-MMP variant suggests multiple forms of this protein may play roles in neurogenesis and adult neuroplasticity.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Membrane-type 5 matrix metalloproteinase (MT5-MMP) is crucial during brain development and in adult neuroplasticity.
  • Its expression patterns in the central nervous system are not fully understood.
  • The multipotent NT2 cell model offers a platform to study neurogenesis and MT5-MMP expression.

Purpose of the Study:

  • To investigate the expression and potential novel forms of MT5-MMP in human neural cells and brain tissue.
  • To characterize the differential expression of MT5-MMP during neurogenesis.
  • To identify any new transcripts or protein variants of MT5-MMP.

Main Methods:

  • Utilized the NT2 cell model for studying neurogenesis and differentiation.
  • Performed mRNA level analysis (e.g., quantitative PCR) to assess MT5-MMP expression.
  • Cloned MT5-MMP cDNA from NT2 cells to identify sequence variations.
  • Conducted in vitro translation and protein detection assays.
  • Analyzed human brain tissue samples (adult hippocampus) and cell lines (NT2, hNT).

Main Results:

  • MT5-MMP mRNA levels were significantly higher in differentiated neuronal hNT cells compared to NT2 cells.
  • A novel MT5-MMP variant (MT5-MMPvar) with a 162bp deletion was identified in NT2 cells.
  • Both standard MT5-MMP and MT5-MMPvar transcripts were found in NT2, hNT cells, and adult human hippocampus.
  • MT5-MMPvar was translated in vitro into a protein of approximately 55 kDa and detected in neural cells and brain tissue.

Conclusions:

  • The human central nervous system may express more than one transcript of MT5-MMP.
  • The novel MT5-MMPvar transcript and its protein product are present in neural cells and adult hippocampus.
  • These findings suggest a more complex role for MT5-MMP in neural function and plasticity than previously recognized.

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