Involvement of ST6Gal I‐mediated α2,6 sialylation in myoblast proliferation and differentiation

Abstract

Myogenesis is a physiological process which involves the proliferation of myoblasts and their differentiation into multinucleated myotubes, which constitute the future muscle fibers. Commitment of myoblasts to differentiation is regulated by the balance between the myogenic factors Pax7 and MyoD. The formation of myotubes requires the presence of glycans, especially N‐glycans, on the cell surface. We examined here the involvement of α2,6 sialylation during murine myoblastic C2C12 cell differentiation by generating a st6gal1‐knockdown C2C12 cell line; these cells exhibit reduced proliferative potential and precocious differentiation due to the low expression of Pax7. The earlier fusion of st6gal1‐knockdown cells leads to a high fusion index and a drop in reserve cells (Pax7+/MyoD−). In st6gal1‐knockdown cells, the Notch pathway is inactivated; consequently, Pax7 expression is virtually abolished, leading to impairment of the proliferation rate. All these results indicate that the decrease in α2,6 sialylation of N‐glycans favors the differentiation of most cells and provokes a significant loss of reserve cells.

The Distinct Roles of Sialyltransferases in Cancer Biology and Onco-Immunology

“…Silencing of ST6Gal1 in prostate cancer cell lines resulted in decreased expression of components of the PI3K/Akt and bcatenin signaling pathways, resulting in reduced proliferation, migration and invasion (122). Furthermore, ST6Gal1 expression is associated with nonmalignant stem and progenitor cells, but also with stemness in cancer and may drive cancer stem cell (CSC)-like characteristics (131)(132)(133)(134)(135)(136). Furthermore, high expression of ST6GAL1 in CSCs could eventually promote chemo-resistance (137).…”

Current Thoughts of Notch’s Role in Myoblast Regulation and Muscle-Associated Disease

“…Unique models of Notch inhibition exemplify inhibited proliferation yet accelerated differentiation of myoblasts [ 22 , 24 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Our laboratory and others have shown promotion of differentiation and impediment of proliferation in the presence of the gamma secretase inhibitors L-685,458 and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester) (DAPT), including a 30% increase in MHC-positive C2C12 myogenic cells and a decrease in the cell cycle progression from G0/G1 to S phase [ 20 , 26 , 31 ].…”

“…Sialylation is active during myoblast proliferation and is decreased during differentiation [ 38 ]. Inhibiting sialylation by downregulating α2,6 sialytransferase activity through generation of an st6gal1-knockdown C2C12 cell line results in decreased myoblast proliferation coupled with less Pax7 and a 70% decline in Notch signaling while initiating earlier differentiation [ 32 ]. Table 1 displays the literature on models used to study the role of Notch in myoblast proliferation and differentiation.…”

Genome-Wide Association Analysis and Genomic Prediction of Thyroglobulin Plasma Levels

“…Sialylation is a late post-translational modification of Tg that occurs in the Golgi apparatus [1]. ST6GAL1 (β-galactoside α-2,6-sialyltransferase), also known as sialyltransferase 1, catalyzes the addition of α-2,6 bound sialic acid to N-glycosylated proteins [9]. It is involved in the sialylation of Tg since α-2,6 bound sialic acid residues are detected at Tg [10,11].…”