MARCKS
Description
The MARCKS (myristoylated alanine rich protein kinase C substrate) is a protein-coding gene located on chromosome 6.
Myristoylated alanine-rich C-kinase substrate is a protein that in humans is encoded by the MARCKS gene. It plays important roles in cell shape, cell motility, secretion, transmembrane transport, regulation of the cell cycle, and neural development. Recently, MARCKS has been implicated in the exocytosis of a number of vesicles and granules such as mucin and chromaffin. It is also the name of a protein family, of which MARCKS is the most studied member. They are intrinsically disordered proteins, with an acidic pH, with high proportions of alanine, glycine, proline, and glutamic acid. They are membrane-bound through a lipid anchor at the N-terminus, and a polybasic domain in the middle. They are regulated by Ca2+/calmodulin and protein kinase C. In their unphosphorylated form, they bind to actin filaments, causing them to crosslink, and sequester acidic membrane phospholipids such as PIP2. The protein encoded by this gene is a substrate for protein kinase C. It is localized to the plasma membrane and is an actin filament crosslinking protein. Phosphorylation by protein kinase C or binding to calcium-calmodulin inhibits its association with actin and with the plasma membrane, leading to its presence in the cytoplasm. The protein is thought to be involved in cell motility, phagocytosis, membrane trafficking and mitogenesis.
MARCKS, a membrane-associated protein, is involved in various cellular processes, including:
- Structural modulation of the actin cytoskeleton, influencing cell shape, movement, and adhesion.
- Chemotaxis and motility, guiding cell migration and movement.
- Phagocytosis, engulfing foreign particles.
- Exocytosis, releasing substances outside the cell.
These functions are achieved through lipid sequestration and protein docking to membranes. MARCKS also plays a crucial role in:
- Embryonic development, tissue regeneration, neuronal plasticity, and inflammation.
- Inhibition of exocytosis by sequestering phosphatidylinositol 4,5-bisphosphate (PIP2) at lipid rafts in the plasma membrane of quiescent cells. This action is reversed by protein kinase C.
- Inflammation, by promoting the migration and adhesion of inflammatory cells and the secretion of cytokines like tumor necrosis factor (TNF), particularly in macrophages.
- Bacteria-induced intracellular reactive oxygen species (ROS) formation in the monocytic cell type.
- Neurite initiation and outgrowth, interacting with components of cellular machinery like CDC42, which regulates cell shape and process extension.
- Axon development by mediating docking and fusion of RAB10-positive vesicles with the plasma membrane.
MARCKS interacts with CDC42, the GTP-bound form of RAB10, and calmodulin/CALM1.
MARCKS is also known as 80K-L, MACS, PKCSL, PRKCSL.
