Discs large homolog 1 (DLG1), also known as synapse-associated protein 97 or SAP97, is a
scaffold protein
In biology, scaffold proteins are crucial regulators of many key signalling pathways. Although scaffolds are not strictly defined in function, they are known to interact and/or bind with multiple members of a signalling pathway, tethering them in ...
that in humans is encoded by the ''SAP97''
gene
In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...
.
SAP97 is a mammalian
MAGUK-family member protein that is similar to the Drosophila protein
Dlg1 (the protein is alternatively referred to as hDlg1, and the human gene is DLG1). SAP97 is expressed throughout the body in
epithelial
Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...
cells. In the brain it is involved in the trafficking of
ionotropic receptors
Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...
from the
endoplasmic reticulum
The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...
to the
plasma membrane
The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...
, and may be involved in the trafficking
AMPAR during synaptic plasticity.
Function
SAP97 is expressed throughout the body in epithelial cells, including the kidney and brain.
There is some evidence that SAP97 regulates cell-to-cell adhesion during cell death, and may interact with
HPV
Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and ...
. In the brain, SAP97's function is involved in the trafficking of transmembrane receptors from the ER to the plasma membrane.
SAP97's function has been investigated by reducing its expression by
knockout
A knockout (abbreviated to KO or K.O.) is a fight-ending, winning criterion in several full-contact combat sports, such as boxing, kickboxing, Muay Thai, mixed martial arts, karate, some forms of taekwondo and other sports involving striking, ...
or increasing its expression
heterologous
The term heterologous has several meanings in biology.
Gene expression
In cell biology and protein biochemistry, heterologous expression means that a protein is experimentally put into a cell that does not normally make (i.e., express) that ...
ly. Mice in which the SAP97 gene has been knocked out die perinatally, have a
cleft palate
A cleft lip contains an opening in the upper lip that may extend into the nose. The opening may be on one side, both sides, or in the middle. A cleft palate occurs when the palate (the roof of the mouth) contains an opening into the nose. The ...
, and deficiencies in renal function.
of SAP97 in mammalian neurons leads to increased
synaptic strength.
Clinical significance
Mutations in DLG1 are associated to
Crohn's disease
Crohn's disease is a type of inflammatory bowel disease (IBD) that may affect any segment of the gastrointestinal tract. Symptoms often include abdominal pain, diarrhea, fever, abdominal distension, and weight loss. Complications outside of the ...
.
Structure
SAP97's protein structure consists of an alternatively-spliced N-terminal domain, three
PDZ domain
The PDZ domain is a common structural domain of 80-90 Amino acid, amino-acids found in the Signal transduction, signaling proteins of bacteria, yeast, plants, viruses and animals. Proteins containing PDZ domains play a key role in anchoring recept ...
s, an
SH3 domain
The SRC Homology 3 Domain (or SH3 domain) is a small protein domain of about 60 amino acid residues. Initially, SH3 was described as a conserved sequence in the viral adaptor protein v-Crk. This domain is also present in the molecules of ph ...
, hook domain, I3 domain, and finally an inactive
guanylate kinase (GK) domain. Each of these domains has specific interacting partners that help define SAP97's unique function.
The N-terminal of SAP97 can be alternatively spliced to contain a double-cysteine/palmitoylation site (α-isoform), or an L27 domain (β-isoform. The L27 domain is involved in SAP97
oligomerization
In chemistry and biochemistry, an oligomer () is a molecule that consists of a few repeating units which could be derived, actually or conceptually, from smaller molecules, monomers.Quote: ''Oligomer molecule: A molecule of intermediate relativ ...
with other SAP97 molecules, CASK, and other L27-domain-containing proteins.
There is also a
myosin
Myosins () are a Protein family, family of motor proteins (though most often protein complexes) best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are adenosine triphosphate, ATP- ...
VI binding site near N-terminal which may be involved in the internalization of AMPAR.
Each of SAP97's PDZ domains have different binding partners, including the AMPAR subunit GluR1
for the first PDZ domain, and
neuroligin
Neuroligin (NLGN), a Transmembrane protein, type I membrane protein, is a Cell adhesion molecule, cell adhesion protein on the Chemical synapse#Structure, postsynaptic membrane that mediates the formation and maintenance of synapses betwee ...
for the last. SAP97's I3 domain is unique to SAP97 among the MAGUK family, and is known to regulate the post-synaptic localization of SAP97
and to bind the protein 4.1N. The GK domain allows SAP97 to bind to
GKAP/SAPAP-family proteins.
References
Further reading
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External links
''Drosophila'' ''discs large 1'' - The Interactive Fly
{{PDB Gallery, geneid=1739