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TMEM2: A missing link in hyaluronan catabolism identified?

Yu Yamaguchi1, Hayato Yamamoto1, Yuki Tobisawa1

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Matrix Biology : Journal of the International Society for Matrix Biology
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Transmembrane 2 (TMEM2) is identified as a potent cell surface hyaluronidase, potentially resolving the long-standing question of how hyaluronan (HA) is initially cleaved in the extracellular space for degradation.

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Glycobiology

Background:

  • Hyaluronan (HA) is a large glycosaminoglycan crucial for tissue structure and turnover.
  • Current models suggest cell surface hyaluronidases initiate HA breakdown, followed by lysosomal degradation.
  • The precise identity of the cell surface hyaluronidase has remained elusive.

Purpose of the Study:

  • To identify the hyaluronidase responsible for the initial cleavage of hyaluronan (HA) on the cell surface.
  • To investigate the role of transmembrane 2 (TMEM2) in hyaluronan catabolism.

Main Methods:

  • Biochemical and enzymological characterization of HYAL proteins.
  • Identification and functional analysis of cell surface proteins with hyaluronidase activity.

Main Results:

  • HYAL family hyaluronidases have roles in HA catabolism but may not be the primary cell surface enzyme.
  • Transmembrane 2 (TMEM2) exhibits potent cell surface hyaluronidase activity.
  • TMEM2 is proposed as the missing hyaluronidase for initial HA cleavage.

Conclusions:

  • TMEM2 is a strong candidate for the elusive cell surface hyaluronidase initiating hyaluronan breakdown.
  • The discovery necessitates updating models of hyaluronan catabolism to include TMEM2.