Shtn1
Developmental stage
Expressed in the developing brain. Expressed in the developing cortical plate at 11 and 14 dpc. Expressed in multipolar cells at 14 dpc (at protein level). Expressed in the developing cortical plate of the telencephalon (PubMed:23864681).
Domain
The N-terminus region is necessary for interaction with actin retrograde filament flow and accumulation in neuronal growth cones.
Function
Involved in the generation of internal asymmetric signals required for neuronal polarization and neurite outgrowth (PubMed:23864681). Mediates netrin-1-induced F-actin-substrate coupling or 'clutch engagement' within the axon growth cone through activation of CDC42, RAC1 and PAK1-dependent signaling pathway, thereby converting the F-actin retrograde flow into traction forces, concomitantly with filopodium extension and axon outgrowth. Plays a role in cytoskeletal organization by regulating the subcellular localization of phosphoinositide 3-kinase (PI3K) activity at the axonal growth cone. Also plays a role in regenerative neurite outgrowth (By similarity). In the developing cortex, cooperates with KIF20B to promote both the transition from the multipolar to the bipolar stage and the radial migration of cortical neurons from the ventricular zone toward the superficial layer of the neocortex (PubMed:23864681). Involved in the accumulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in the growth cone of primary hippocampal neurons (PubMed:23864681).
Post-translational modifications
Phosphorylated on Ser-101 and Ser-249 by PAK1 through a CDC42- and RAC1-dependent signaling pathway, which enhances its association with F-actin retrograde flow in filopodia and lamellipodia of axonal growth cones. Phosphorylation on Ser-101 and Ser-249 is increased by netrin-1.
Sequence Similarities
Belongs to the shootin family.
Tissue Specificity
Expressed in hippocampal neurons (PubMed:17030985).
Cellular localization
- Perikaryon
- Cell projection
- Axon
- Cell projection
- Growth cone
- Cytoplasm
- Cytoskeleton
- Cell projection
- Filopodium
- Cell projection
- Lamellipodium
- Localizes in multiple growth cones at neurite tips before the neuronal symmetry-breaking step. Accumulates in growth cones of a single nascent axon in a neurite length-dependent manner during the neuronal symmetry-breaking step; when absent from the nascent axon's siblings, probably due to competitive transport, prevents the formation of surplus axons. Transported anterogradely from the soma to the axon growth cone in an actin and myosin-dependent manner and passively diffuses back to the cell bodies. Colocalized with L1CAM in close apposition with actin filaments in filopodia and lamellipodia of axonal growth cones in hippocampal neurons. Exhibits retrograde movements in filopodia and lamellopodia of axonal growth cones (By similarity). Colocalized with KIF20B along microtubules to the tip of the growing cone in primary hippocampal neurons (PubMed:23864681). Recruited to the growth cone of developing axon in a KIF20B- and microtubule-dependent manner (PubMed:23864681).
Alternative names
Kiaa1598, Shootin-1, Shootin1