SYNPO2
Developmental stage
Detected in myoblasts within 24 hours after induction of myogenic differentiation preceeding the expression of sarcomeric alpha-actinin. Specifically at early stages colocalizes with ZYX at focal adhesions.
Domain
The PPPY motif interacts with the WW domain 1 of BAG3.
Function
Has an actin-binding and actin-bundling activity. Can induce the formation of F-actin networks in an isoform-specific manner (PubMed:23225103, PubMed:24005909). At the sarcomeric Z lines is proposed to act as adapter protein that links nascent myofibers to the sarcolemma via ZYX and may play a role in early assembly and stabilization of the Z lines. Involved in autophagosome formation. May play a role in chaperone-assisted selective autophagy (CASA) involved in Z lines maintenance in striated muscle under mechanical tension; may link the client-processing CASA chaperone machinery to a membrane-tethering and fusion complex providing autophagosome membranes (By similarity). Involved in regulation of cell migration (PubMed:22915763, PubMed:25883213). May be a tumor suppressor (PubMed:16885336).
Isoform 1
Involved in regulation of cell migration. Can induce formation of thick, irregular actin bundles in the cell body.
Isoform 2
Involved in regulation of cell migration. Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers.
Isoform 3
Involved in regulation of cell migration. Can induce an amorphous actin meshwork throughout the cell body containing a mixture of long and short, randomly organized thick and thin actin bundles.
Isoform 4
Can induce long, well-organized actin bundles frequently orientated in parallel along the long axis of the cell showing characteristics of contractile ventral stress fibers.
Isoform 5
Involved in regulation of cell migration in part dependent on the Rho-ROCK cascade; can promote formation of nascent focal adhesions, actin bundles at the leading cell edge and lamellipodia (PubMed:22915763, PubMed:25883213). Can induce formation of thick, irregular actin bundles in the cell body; the induced actin network is associated with enhanced cell migration in vitro.
Post-translational modifications
Phosphorylated by PKA, and by CaMK2 at multiple sites. Dephosphorylated by calcineurin; abrogating interaction with YWHAB and impairing nuclear import (By similarity). Phosphorylated by ILK.
Sequence Similarities
Belongs to the synaptopodin family.
Tissue Specificity
Expressed in heart muscle. Isoform 5 is specifically expressed in skeletal muscle.
Cellular localization
- Nucleus
- Cytoplasm
- Cytoplasm
- Cytoskeleton
- Cytoplasm
- Myofibril
- Sarcomere
- Z line
- Cell junction
- Focal adhesion
- Shuttles between the nucleus and the cytoplasm in a differentiation-dependent and stress-induced fashion. In undifferentiated myoblasts strongly expressed in the nucleus, after induction of myotube differentiation is located to both nucleus and cytoplasm along acting filaments, and in differentiated myotubes is located at the Z lines. Upon stress redistributes from cytoplasm of myoblasts and myotubes to the nucleus. Nuclear import is KPNA2-dependent and promoted by phosphorylation by PKA and/or CaMK2, and inhibition of calcineurin. The nuclear export is XPO1-dependent (By similarity). Localized in a fiber-like pattern, partly overlapping with filamentous actin (PubMed:18371299).
- Isoform 1
- Cytoplasm
- Cytoskeleton
- Localizes to induced actin bundles with contiguous staining.
- Isoform 2
- Cytoplasm
- Cytoskeleton
- Localizes to induced actin bundles with punctuate staining.
- Isoform 3
- Cytoplasm
- Cytoskeleton
- Localizes to induced irregular actin bundles with contiguous and punctuated staining.
- Isoform 4
- Cytoplasm
- Cytoskeleton
- Localizes to induced actin bundles with punctuate staining.
- Isoform 5
- Cytoplasm
- Cytoskeleton
- Localizes to induced actin bundles with contiguous staining.
Alternative names
Synaptopodin-2, Genethonin-2, Myopodin, SYNPO2