GLYPICAN 4

Official Full Name

glypican 1

Organism

Homo sapiens

Gene ID

2817

Background

Cell surface heparan sulfate proteoglycans are composed of a membrane-associated protein core substituted with a variable number of heparan sulfate chains. Members of the glypican-related integral membrane proteoglycan family (GRIPS) contain a core protein anchored to the cytoplasmic membrane via a glycosyl phosphatidylinositol linkage. These proteins may play a role in the control of cell division and growth regulation. [provided by RefSeq, Jul 2008]

Synonyms

GPC1; glypican

Clones

Cat.No.	Product Name	Price
CDCL184423	Human glypican 4 ORF clone(NM_001448.2)	Inquiry

Detailed Information

Glypicans are a family of heparan sulfate proteoglycans that are linked to the external surface of the plasma membrane through a glycosylphosphatidylinositol (GPI) anchor. Glypicans can bind multiple soluble and insoluble ligands. Moreover, they are shed from the cell surface into extracellular space by the lipase-mediated cleavage of a GPI anchor. These indicate that glypicans can play a role not only in the cell membrane, but also in the extracellular environment including the circulation and remote tissues. Generally, glypicans are thought to contribute to cellular proliferation and tissue growth by modifying cell signaling pathways of wingless-type MMTV integration site family members (Wnts), Hedgehogs, fibroblast growth factors and bone morphogenetic proteins. In mammals, the glypican family has six members (glypican-1 to glypican-6).

Glypican-4 is ordinarily a membrane-bound hormone, owing to a GPI anchor. Nevertheless, this anchor can be cleaved, allowing glypican-4 to be secreted. The researchers have previously shown that glypican-4 is differentially expressed in visceral and subcutaneous adipose tissue of humans and mice. Furthermore, there was a very strong correlation of glypican-4 expression with body mass index (BMI) and waist-to-hip ratio (WHR). Recently, the investigators found that cultured murine preadipocytes lacking glypican-4 failed to differentiate into adipocytes or to accumulate fat when stimulated to do so with a standard cocktail of drugs. Closer investigation revealed that induction of key adipogenic transcription factors such as PPAR-γ and C/EBPα was disrupted. However, when glypican-4 expression was restored, differentiation was rescued and expression of these key transcription factors was increased. This effect was independent of the integrity of the GPI anchor, suggesting that glypican-4 can influence adipogenesis in both its membrane-bound and secreted forms.

Glypican-4 appears to play its effects by influencing insulin signalling. Overexpression of glypican-4 or the addition of recombinant ectodomain of glypican-4 enhanced insulin signaling in cultured adipocytes, whereas depletion of glypican-4 reduced insulin receptor phosphorylation and the following downstream signaling. In adipocytes, glypican-4 plays a key role for adipocyte differentiation through insulin-mediated CCAAT/enhancer binding protein-β (CEBPβ) phosphorylation, which is essential for transactivation of CEBPα and peroxisome proliferator-activated receptor-γ (PPARγ), the key transcriptional factors required for adipocyte differentiation. Moreover, the released ectodomain of glypican-4 is also suggested to enhance insulin signaling as an adipokine in the liver and skeletal muscle.

Glypican‐4.jpg

Figure 1. Glypican-4 promotes adipocyte differentiation and enhances insulin receptor signaling in the liver and skeletal muscle.

In addition, low serum levels of glypican-4 were associated with insulin resistance in humans. Insulin resistance is characterized by a drop in circulating insulin levels. Cleavage of the GPI anchor could be regulated by insulin and so, during the development of insulin resistance, insulin and glypican-4 levels would both fall. This compound effect might accelerate disease progression. Therefore, maintaining serum levels of glypican-4 in people with insulin resistance or diabetes mellitus could reduce their need for insulin therapy.

References:

Yoo H J, et al. Association of glypican-4 with body fat distribution, insulin resistance, and nonalcoholic fatty liver disease. Journal of Clinical Endocrinology & Metabolism, 2013, 98(7):2897-2901.
Tamori Y, Kasuga M. Glypican-4 is a new comer of adipokines working as insulin sensitizer. Journal of Diabetes Investigation, 2013, 4(3):250-251.
Mitchell F. Glypican-4: role in insulin signalling. Nature Reviews Endocrinology, 2012, 8(9): 505-506.

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