PDLIM4
Function
Isoform 1
Suppresses SRC activation by recognizing and binding to active SRC and facilitating PTPN13-mediated dephosphorylation of SRC 'Tyr-419' leading to its inactivation. Inactivated SRC dissociates from this protein allowing the initiation of a new SRC inactivation cycle (PubMed:19307596). Involved in reorganization of the actin cytoskeleton (PubMed:21636573). In nonmuscle cells, binds to ACTN1 (alpha-actinin-1), increases the affinity of ACTN1 to F-actin (filamentous actin), and promotes formation of actin stress fibers. Involved in regulation of the synaptic AMPA receptor transport in dendritic spines of hippocampal pyramidal neurons directing the receptors toward an insertion at the postsynaptic membrane. Links endosomal surface-internalized GRIA1-containing AMPA receptors to the alpha-actinin/actin cytoskeleton. Increases AMPA receptor-mediated excitatory postsynaptic currents in neurons (By similarity).
Isoform 2
Involved in reorganization of the actin cytoskeleton and in regulation of cell migration. In response to oxidative stress, binds to NQO1, which stabilizes it and protects it from ubiquitin-independent degradation by the core 20S proteasome. Stabilized protein is able to heterodimerize with isoform 1 changing the subcellular location of it from cytoskeleton and nuclei to cytosol, leading to loss of isoforms 1 ability to induce formation of actin stress fibers. Counteracts the effects produced by isoform 1 on organization of actin cytoskeleton and cell motility to fine-tune actin cytoskeleton rearrangement and to attenuate cell migration.
Post-translational modifications
Phosphorylated on tyrosine residue(s). Can be dephosphorylated by PTPN13.
Tissue Specificity
Isoform 2
Found in brain.
Cellular localization
- Isoform 1
- Cytoplasm
- Cytoskeleton
- Nucleus
- Cytoplasm
- Cytoplasm
- Perinuclear region
- Cell projection
- Lamellipodium
- Cell projection
- Dendritic spine
- Early endosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Recycling endosome membrane
- Peripheral membrane protein
- Cytoplasmic side
- Synapse
- Synaptosome
- Localizes to actin stress fibers in nonmuscle cells. Colocalizes with GRIA1 in early endosomes. Enriched in numerous but not all spine-like structures along dendritic branches. Colocalizes with actin and enriched at sites containing larger amounts of actin and alpha-actinin. Targeted efficiently to spines via its PDZ domain-mediated interaction with the alpha-actinin/actin cytoskeletal complex. Localizes to synaptosomes in brain (By similarity). Colocalizes with F-actin (PubMed:10826496). Colocalizes with TRIP6 at cell-cell contacts and lamellipodia (PubMed:10826496). In the cytoplasm, displays a fibrillar pattern with characteristic thick fibers and occasional clusters. Colocalizes with the actin stress fibers. Oxidative stress induces redistribution from cytoskeleton to cytosol (PubMed:21636573). Colocalizes with SRC at the perinuclear region, but not at focal adhesions (PubMed:19307596).
- Isoform 2
- Cytoplasm
- Stains more diffusely in the cytoplasm with thin fibers forming a dense mesh-like pattern.
Alternative names
RIL, PDLIM4, PDZ and LIM domain protein 4, LIM protein RIL, Reversion-induced LIM protein