Protein tyrosine phosphatases ε and α perform nonredundant roles in osteoclasts

Eynat Finkelshtein, Sutada Lotinun, Einat Levy-Apter, Esther Arman, Jeroen den Hertog, Roland Baron, Ari Elson

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

Female mice lacking protein tyrosine phosphatase ε (PTP ε) are mildly osteopetrotic. Osteoclasts from these mice resorb bone matrix poorly, and the structure, stability, and cellular organization of their podosomal adhesion structures are abnormal. Here we compare the role of PTP ε with that of the closely related PTP α in osteoclasts. We show that bone mass and bone production and resorption, as well as production, structure, function, and podosome organization of osteoclasts, are unchanged in mice lacking PTP α. The varying effects of either PTP on podosome organization in osteoclasts are caused by their distinct N-termini. Osteoclasts express the receptor-type PTP α (RPTPa), which is absent from podosomes, and the nonreceptor form of PTP ε (cyt-PTPe), which is present in these structures. The presence of the unique 12 N-terminal residues of cyt-PTPe is essential for podosome regulation; attaching this sequence to the catalytic domains of PTP α enables them to function in osteoclasts. Serine 2 within this sequence regulates cyt-PTPe activity and its effects on podosomes. We conclude that PTPs α and ε play distinct roles in osteoclasts and that the N-terminus of cyt-PTPe, in particular serine 2, is critical for its function in these cells.

Original languageEnglish
Pages (from-to)1808-18
Number of pages11
JournalMolecular Biology of the Cell
Volume25
Issue number11
DOIs
Publication statusPublished - Jun 2014

Keywords

  • Amino Acid Sequence
  • Animals
  • Collagen Type I
  • Female
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Osteoclasts
  • Peptides
  • Phosphorylation
  • Receptor-Like Protein Tyrosine Phosphatases, Class 4
  • Serine
  • Tibia
  • src-Family Kinases

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