A mammalian homolog of the zebrafish transmembrane protein 2 (TMEM2) is the long-sought-after cell-surface hyaluronidase

摘要: Hyaluronan (HA) is an extremely large polysaccharide (glycosaminoglycan) involved in many cellular functions. HA catabolism thought to involve the initial cleavage of extracellular high-molecular-weight (HMW) into intermediate-size by or cell-surface hyaluronidase, internalization HA, and complete degradation monosaccharides lysosomes. Despite considerable research, identity hyaluronidase responsible for space remains elusive. HYAL1 HYAL2 have properties more consistent with lysosomal hyaluronidases, whereas CEMIP/KIAA1199, a recently identified HA-binding molecule that has HA-degrading activity, requires participation clathrin-coated pit pathway live cells degradation. Here we show transmembrane protein 2 (TMEM2), mammalian homolog playing role zebrafish endocardial cushion development, hyaluronidase. Live immunostaining surface biotinylation assays confirmed mouse TMEM2 expressed on cell type II topology. degraded HMW-HA ∼5-kDa fragments but did not cleave chondroitin sulfate dermatan sulfate, indicating its specificity HA. The activity was Ca2+-dependent; enzyme's pH optimum around 6–7, unlike does require activity. Moreover, TMEM2-expressing could eliminate immobilized glass contact-dependent manner. Together, these data suggest long-sought-after cleaves before lysosome.