Role in Cell Migration
Neural precursors are generated in proliferative zones, before migrating to directed locations where they undergo maturation and become functional neurons. Studies in Drosophilia first suggested Numb played a role in cell migration when mutants displayed defective glial migration along axonal tracts. Since then, a mechanism has been discovered through which Numb binds chemotactic signaling receptors, forming a scaffold for atypical PKC (aPKC) recruitment to the receptor complex. Once activated, aPKC phosphorylates Numb, thus promoting a positive feed-forward response that potentiates Numb-chemotactic receptor binding and subsequent endosomal complex formation. Endocytosis supports the relocalization of the chemotactic receptor to the front of the cell to promote receptor-mediated directional migration in response to receptor activation.
Brain-derived neurotrophic factor is among the chemotactic factors that stimulate Numb-mediated chemotaxis during cell migration. BDNF can function as a chemotactic factor for neural precursors during migration by activating TrkB receptors. Numb binds to TrkB receptors to act as an endocytic regulator of TrkB and promote aPKC activation by acting as a scaffolding protein. Once phosphorylated, aPKC can also phosphorylate Numb to increase its efficacy for binding TrkB, thus promoting the precursor’s chemotactic sensitivity to BDNF.
Read more about this topic: NUMB (gene)
Famous quotes containing the words role in, role and/or cell:
“Language makes it possible for a child to incorporate his parents’ verbal prohibitions, to make them part of himself....We don’t speak of a conscience yet in the child who is just acquiring language, but we can see very clearly how language plays an indispensable role in the formation of conscience. In fact, the moral achievement of man, the whole complex of factors that go into the organization of conscience is very largely based upon language.”
—Selma H. Fraiberg (20th century)
“So successful has been the camera’s role in beautifying the world that photographs, rather than the world, have become the standard of the beautiful.”
—Susan Sontag (b. 1933)
“I turn and turn in my cell like a fly that doesn’t know where to die.”
—Antonio Gramsci (1891–1937)