SLC2A11 (GLUT11) as mannose preferential transporter (607.15)

Abstract

Most studies of hexose transporters (GLUT family) focus on glucose and fructose import for energy generation. Few studies examine their role in delivering sugars for biosynthetic pathways. Exogenous mannose can directly contribute nearly 50% of the mannose found in glycoproteins, even though its extracellular concentration (50 µM) is 100‐fold lower than physiological glucose (5mM). To explain this preference, we hypothesized the existence of a high affinity mannose‐preferential hexose transporter. We identified a patient with damaging mutation in SLC2A11 (Glucose transporter, GLUT11) and applied our new GC‐MS method to determine the contributions of 13C‐glucose and 13C‐mannose to N‐glycans. Patient fibroblasts showed reduced direct contribution of mannose, prompting us to investigate GLUT 11 as potential mannose transporter. RNAi knockdown of GLUT11 confirmed that it directly contributes mannose to N‐glycans , especially at the physiological range (50 µM) suggesting that GLUT11 has low Kuptake for mannose. The reported Km for glucose is 160µM. Preliminary results show that knockdown of GLUT 1 has no effect on mannose flux into N‐glycans. We suggest that GLUT11 is the first mannose‐preferential transporter for N‐glycan synthesis. Other mannose preferential transporters may exist.Grant Funding Source: R01DK55615 and The Rocket Fund