GLUT8

GLUT8 also known as SLC2A8 is the eighth member of glucose transporter superfamily.[1]

solute carrier family 2, (facilitated glucose transporter) member 8
Identifiers
SymbolSLC2A8
Alt. symbolsGLUTX1, GLUT8
NCBI gene29988
HGNC13812
OMIM605245
RefSeqNM_014580
Other data
LocusChr. 9 q33.3

It is characterized by the presence of two leucine residues in its N-terminal intracellular domain, which influences intracellular trafficking.[2]

Discovery

GLUT8, originally named GLUTX1, was cloned almost simultaneously by two different groups.[2][3]

Tissue distribution

Subcellular localization

Contrary to GLUT4, GLUT8 (previously known as GLUTX1) is not insulin-sensitive. In other words, insulin does not promote GLUT8 translocation to the cell surface in neurons as well as in transfected cell lines.

Where in the cell GLUT8 is localized in not yet clear. Most GLUT8 is not present at the cell surface. Some co-localization with both the endoplasmic reticulum and late endosomes/lysosomes has been published.[4]

When the N-terminal di-leucine motif is mutated into a di-alanine motif, GLUT8 is located mostly at the cell surface in Xenopus oocytes and mammalian cells such as HEK 293 cells and differentiated PC12 cells.

Physiological role

GLUT8 function in vivo remains to be defined, despite suggestions that it may play a role in fertility, being expressed at high levels in testes and in the acrosomal part of spermatozoa.[5] Furthermore, GLUT8 appears to play an important role in the energy metabolism of sperm cells.[6]

GLUT8, when expressed in Xenopus oocytes, mediates glucose uptake with high affinity. Other hexoses are not good substrates of the transporter.

Mice devoid of both copies of the SLC2A8 gene are viable, fertile and do not show any obvious phenotype.[7] They are not diabetic, showing that GLUT8 is unlikely to play major roles in glucose homeostasis.

References
  1. Uldry M, Thorens B (February 2004). "The SLC2 family of facilitated hexose and polyol transporters" (PDF). Pflügers Arch. 447 (5): 480–9. doi:10.1007/s00424-003-1085-0. PMID 12750891. S2CID 25539725.
  2. Ibberson M, Uldry M, Thorens B (2000). "GLUTX1, a novel mammalian glucose transporter expressed in the central nervous system and insulin-sensitive tissues". J. Biol. Chem. 275 (7): 4607–12. doi:10.1074/jbc.275.7.4607. PMID 10671487.
  3. Doege H, Schürmann A, Bahrenberg G, Brauers A, Joost HG (2000). "GLUT8, a novel member of the sugar transport facilitator family with glucose transport activity". J. Biol. Chem. 275 (21): 16275–80. doi:10.1074/jbc.275.21.16275. PMID 10821868.
  4. Widmer M, Uldry M, Thorens B (2005). "GLUT8 subcellular localization and absence of translocation to the plasma membrane in PC12 cells and hippocampal neurons". Endocrinology. 146 (11): 4727–36. doi:10.1210/en.2005-0668. PMID 16109784.
  5. Schürmann A, Axer H, Scheepers A, Doege H, Joost HG (February 2002). "The glucose transport facilitator GLUT8 is predominantly associated with the acrosomal region of mature spermatozoa". Cell Tissue Res. 307 (2): 237–42. doi:10.1007/s00441-001-0499-2. PMID 11845330. S2CID 20138373.
  6. Gawlik V, Schmidt S, Scheepers A, Wennemuth G, Augustin R, Aumüller G, Moser M, Al-Hasani H, Kluge R, Joost HG, Schürmann A (April 2008). "Targeted disruption of Slc2a8 (GLUT8) reduces motility and mitochondrial potential of spermatozoa". Mol. Membr. Biol. 25 (3): 224–35. doi:10.1080/09687680701855405. PMC 2557070. PMID 18428038.
  7. Membrez M, Hummler E, Beermann F, Haefliger JA, Savioz R, Pedrazzini T, Thorens B (2006). "GLUT8 is dispensable for embryonic development but influences hippocampal neurogenesis and heart function". Mol. Cell. Biol. 26 (11): 4268–76. doi:10.1128/MCB.00081-06. PMC 1489108. PMID 16705176.
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