GLUT8
Encyclopedia
GLUT8 also known as SLC2A8 is the eighth member of glucose transporter
superfamily.
It is characterized by the presence of two leucine
residues in its N-terminal intracellular domain
, which influences intracellular trafficking
.
s and testis, although expression in most other tissues has also been shown at lower levels. GLUT8 is expressed at moderate levels in the brain, most strikingly in hippocampus
. Whether the glucose transporter plays any role in these cells remains to be shown.
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.
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
.
part of spermatozoa. Furthermore GLUT8 appears to play an important role in the energy metabolism of sperm cells.
The recent description of GLUT8 expression in kidneys and liver suggest that the transporter may play a role in glucose uptake in these organs.
GLUT8, when expressed in Xenopus oocytes, mediates glucose uptake with high affinity. Other hexoses are not good substrates of the transporter. Whether the transporter actually mediates glucose uptake in vivo in the brain has not been evaluated yet.
Mice devoid of both copies of the SLC2A8 gene are viable, fertile and do not show any obvious phenotype
. They are not diabetic, showing that GLUT8 is unlikely to play major roles in glucose homeostasis.
Glucose transporter
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Because glucose is a vital source of energy for all life these transporters are present in all phyla...
superfamily.
It is characterized by the presence of two leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
residues in its N-terminal intracellular domain
Protein domain
A protein domain is a part of protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact three-dimensional structure and often can be independently stable and folded. Many proteins consist of several structural...
, which influences intracellular trafficking
Protein targeting
Protein targeting or protein sorting is the mechanism by which a cell transports proteins to the appropriate positions in the cell or outside of it. Sorting targets can be the inner space of an organelle, any of several interior membranes, the cell's outer membrane, or its exterior via secretion...
.
Discovery
GLUT8, originally named GLUTX1, was cloned almost simultaneously by two different groups.Tissue distribution
GLUT8 is expressed mostly in neuronNeuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s and testis, although expression in most other tissues has also been shown at lower levels. GLUT8 is expressed at moderate levels in the brain, most strikingly in hippocampus
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
. Whether the glucose transporter plays any role in these cells remains to be shown.
Subcellular localization
Contrary to GLUT4, GLUT8 (previously known as GLUTX1) is not insulin-sensitive. In other words, insulin does not promote GLUT8 translocationProtein targeting
Protein targeting or protein sorting is the mechanism by which a cell transports proteins to the appropriate positions in the cell or outside of it. Sorting targets can be the inner space of an organelle, any of several interior membranes, the cell's outer membrane, or its exterior via secretion...
to the cell surface in neurons as well as in transfected
Transfection
Transfection is the process of deliberately introducing nucleic acids into cells. The term is used notably for non-viral methods in eukaryotic cells...
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.
When the N-terminal di-leucine motif is mutated into a di-alanine motif, GLUT8 is located mostly at the cell surface in Xenopus
Xenopus
Xenopus is a genus of highly aquatic frogs native to Sub-Saharan Africa. There are 19 species in the Xenopus genus...
oocytes and mammalian cells such as HEK 293 cells
HEK cell
Human Embryonic Kidney 293 cells, also often referred to as HEK 293, 293 cells, or less precisely as HEK cells are a specific cell line originally derived from human embryonic kidney cells grown in tissue culture. HEK 293 cells are very easy to grow and transfect very readily and have been...
and differentiated PC12 cells
PC12 cells
PC12 is a cell line derived from a pheochromocytoma of the rat adrenal medulla. PC12 cells stop dividing and terminally differentiate when treated with nerve growth factor...
.
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 acrosomalAcrosome
The acrosome is an organelle that develops over the anterior half of the head in the spermatozoa of many animals. It is a cap-like structure derived from the Golgi apparatus. Acrosome formation is completed during testicular maturation. In Eutherian mammals the acrosome contains digestive enzymes...
part of spermatozoa. Furthermore GLUT8 appears to play an important role in the energy metabolism of sperm cells.
The recent description of GLUT8 expression in kidneys and liver suggest that the transporter may play a role in glucose uptake in these organs.
GLUT8, when expressed in Xenopus oocytes, mediates glucose uptake with high affinity. Other hexoses are not good substrates of the transporter. Whether the transporter actually mediates glucose uptake in vivo in the brain has not been evaluated yet.
Mice devoid of both copies of the SLC2A8 gene are viable, fertile and do not show any obvious phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
. They are not diabetic, showing that GLUT8 is unlikely to play major roles in glucose homeostasis.