Pathway: Recycling pathway of L1
Reactions in pathway: Recycling pathway of L1 :
Recycling pathway of L1
L1 functions in many aspects of neuronal development including axon outgrowth and neuronal migration. These functions require coordination between L1 and the actin cytoskeleton. F-actin continuously moves in a retrograde direction from the P-(peripheral) domain of the growth cone towards the growth cone's C-(central) domain. L1, attached to the actin cytoskeleton via membrane cytoskeletal linkers (MCKs) such as ankyrins (Ankyrin-G, -B and -R) and members of the ERMs (ezrin, radixin, and moesin) family, link this retrograde F-actin flow with extracellular immobile ligands.
Forward translocation of growth cone requires not only the CAM-actin linkage but also a gradient of cell substrate adhesion (strong adhesion at the front and weak adhesion at the rear) so that the cytoskeletal machinery is able to pull the cell forward as attachments at the rear are released. This asymmetry is achieved in part by internalizing L1 molecules as they are moved to the rear of the growth cone coupled to retrograde F-actin flow and recycling them to the leading edge plasma membrane.
L1 internalization is mediated by phosphorylation and dephosphorylation. The L1 cytoplasmic domain (L1CD) carries an endocytic or sorting motif, YRSLE, that is recognized by the clathrin associated adaptor protein-2 (AP-2). AP-2 binds the YRSLE motif only when its tyrosine is not phosphorylated and triggers L1 endocytosis. SRC kinase associated with lipid rafts in the P-domain membrane phosphorylates L1 molecules on tyrosine-1176, stabilizing them in the plasma membrane. L1 endocytosis is triggered by the dephosphorylation of Y1176 within the C domain. Some of these internalized L1 molecules are transported in an anterograde direction along microtubules for reuse in the leading edge.
Forward translocation of growth cone requires not only the CAM-actin linkage but also a gradient of cell substrate adhesion (strong adhesion at the front and weak adhesion at the rear) so that the cytoskeletal machinery is able to pull the cell forward as attachments at the rear are released. This asymmetry is achieved in part by internalizing L1 molecules as they are moved to the rear of the growth cone coupled to retrograde F-actin flow and recycling them to the leading edge plasma membrane.
L1 internalization is mediated by phosphorylation and dephosphorylation. The L1 cytoplasmic domain (L1CD) carries an endocytic or sorting motif, YRSLE, that is recognized by the clathrin associated adaptor protein-2 (AP-2). AP-2 binds the YRSLE motif only when its tyrosine is not phosphorylated and triggers L1 endocytosis. SRC kinase associated with lipid rafts in the P-domain membrane phosphorylates L1 molecules on tyrosine-1176, stabilizing them in the plasma membrane. L1 endocytosis is triggered by the dephosphorylation of Y1176 within the C domain. Some of these internalized L1 molecules are transported in an anterograde direction along microtubules for reuse in the leading edge.
Neurogenesis is the process by which neural stem cells give rise to neurons, and occurs both during embryonic and perinatal development as well as in specific brain lineages during adult life (reviewed in Gotz and Huttner, 2005; Yao et al, 2016; Kriegstein and Alvarez-Buylla, 2009).
As early steps towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of several processes have been annotated. Aspects of processes involved in most developmental processes, transcriptional regulation of pluripotent stem cells, gastrulation, and activation of HOX genes during differentiation are annotated. More specialized processes include nervous system development , aspects of the roles of cell adhesion molecules in axonal guidance and myogenesis, transcriptional regulation in pancreatic beta cell, cardiogenesis, transcriptional regulation of granulopoeisis, transcriptional regulation of testis differentiation, transcriptional regulation of white adipocyte differentiation, and molecular events of "nodal" signaling, LGI-ADAM interactions, and keratinization.