Datingpoint ch test
Datingpoint ch test
The collected experimental evidence for Wnt secretion indicates existence of specialized machineries for intracellular transport of Wnt proteins, discarding the idea of a passive flow of Wnts through the secretory pathway.
Both types of post-translational modifications are relevant during Wnt signaling, but they are also important for proper Wnt protein folding and intracellular trafficking .
Although less well studied, it is clear that the non-canonical signaling regulates cell migration and organ morphogenesis through the activation of Ca signaling and cytoskeletal proteins including the small GTPases Rho A, Rac1 and Cdc42, and the kinases ROCK, PKC, and JNK .
Some secreted Wnt proteins such as Wnt1, 3, 3a, 8a and 8b are described to activate exclusively the canonical signaling, whereas Wnt5a, 7a, 7b and 11 have mostly been implicated in the non-canonical pathway .
How Wnt ligands are secreted and how Wnt gradients are formed is currently not well understood and very divergent models explaining these features have been proposed [6,9,10].
In addition to initiation of the Wnt-response programs, the receiving cells play a role in Wnt gradient formation by endocytosis and lysosomal degradation of the morphogen [11,12].
At the Golgi, Wnts are escorted to the plasma membrane (PM) by an evolutionary conserved multipass transmembrane protein called Wntless/Evenness interrupted/Sprinter [13–15] (hereafter-Wntless) which specifically interacts with acylated Wnts .
Once at the PM, Wntless is internalized by the clathrin-mediated endocytosis and is then sorted away from the lysosomal degradation route by the retromer complex .
Here we revise the current views of Wnt secretion and spreading, and propose two models for the role of the reggie/flotillin proteins in these processes: (i) reggies/flotillins regulate the basolateral endocytosis of the poorly diffusible, membrane-bound Wnt pool, which is then sorted and secreted to apical compartments for long-range diffusion, and (ii) lipid rafts organized by reggies/flotillins serve as “dating points” where extracellular Wnt transiently interacts with lipoprotein receptors to allow its capture and further spreading via lipoprotein particles.
We further discuss these processes in the context of human breast cancer.
Cytoplasmic β-catenin levels are regulated through its continuous proteasome-mediated degradation induced by this complex.
When cells receive a Wnt signal, the degradation is inhibited and β-catenin accumulates in the cytoplasm and nucleus.
A better understanding of these phenomena may be relevant for identification of novel drug targets and therapeutic strategies.