.png){kind=icon}
.png){kind=icon}
Return
Regulation of TMEM2-mediated hyaluronan degradation by CD44 and LYVE-1
.png){kind=icon}
OA
AI
Y
F
R
F
T
Y
DOI：10.3389/fmolb.2026.1852012.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Hyaluronan (HA) is a major glycosaminoglycan of the extracellular matrix that regulates cell migration; signaling; and tissue homeostasis. Its turnover is controlled by coordinated synthesis by HA synthases and degradation by hyaluronidases. Among these hyaluronidases; TMEM2; the only known transmembrane hyaluronidase; plays a unique role in HA degradation at the cell surface; however; the cellular conditions that support its activity remain incompletely understood. To address this; we developed a cell-based HA turnover assay to examine TMEM2-mediated degradation of endogenously synthesized HA; rather than exogenously added; fluorescently labeled HA used in previous studies. Using this system; we show that TMEM2 readily degrades high-molecular weight HA synthesized by co-expressed HAS3. This degradation occurs only when TMEM2 and HAS3 are co-expressed in the same cells (cis); whereas co-culture of TMEM2-expressing cells with HAS3-expressing cells supports little or no degradation. Interestingly; HA-binding cell surface receptors CD44 and its homolog LYVE-1 promote efficient TMEM2-mediated HA degradation even under trans conditions; whereas other HA-binding proteins; including TSG-6; layilin; TLR2; RHAMM; and ICAM-1; do not. These findings suggest a spatially regulated mechanism of TMEM2 activity in which capture of HA at the cell surface; mediated by CD44 or LYVE-1; contributes to efficient HA degradation by TMEM2.
Keywords:
CD44
glycocalyx
hyaluronidase
hyaluronan
LYVE-1
TMEM2
Journal
IF:
4
Papers:
6.0K
Citations:
2.0W
Organization
Cited Papers