Disease relevance of PPFIA1

• Liprin-alpha2 gene, protein tyrosine phosphatase LAR interacting protein related gene, is downregulated by androgens in the human prostate cancer cell line LNCaP [1].
• In addition to its nuclear functions, cytoplasmic ING4 interacts with liprin alpha1 to regulate cell migration and, with its known antiangiogenic function, may prevent invasion and metastasis [2].
• A lipase gene (lip1) from the facultative psychrophilic strain Psychrobacter immobilis B10 has been cloned and sequenced [3].

High impact information on PPFIA1

• Synaptic transmission regulated by a presynaptic MALS/Liprin-alpha protein complex [4].
• We propose that the cadherin-beta-catenin complex is cotransported with AMPA receptors to synapses and dendritic spines by a mechanism that involves binding of liprin-alpha to LAR-RPTP and tyrosine dephosphorylation by LAR-RPTP [5].
• Leukocyte common antigen-related (LAR) family receptor protein tyrosine phosphatases (LAR-RPTP) bind to liprin-alpha (SYD2) and are implicated in axon guidance [5].
• The LAR transmembrane protein tyrosine phosphatase and a coiled-coil LAR-interacting protein co-localize at focal adhesions [6].
• We propose that LAR and LIP.1 may regulate the disassembly of focal adhesions and thus help orchestrate cell-matrix interactions [6].

Biological context of PPFIA1

• In further characterizing the phosphorylation of liprin, we found immunoprecipitates of liprin-alpha1 expressed in COS-7 cells to incorporate phosphate after washes of up to 4 M NaCl [7].
• In contrast, overexpressed liprin alpha1 enhanced cell spreading and cell migration [2].
• However, ING4 did not further suppress cell motility when liprin alpha1 was suppressed with RNA interference, suggesting a functional and mechanistic interdependence between these proteins [2].
• We identified additional genes which are involved in different signaling pathways which regulate programmed cell death (Dynamin 2, Pdcd4 and LIP.1) [8].
• The dark-adaptation response of the de-etiolated pea mutant lip1 is modulated by external signals and endogenous programs [9].

Anatomical context of PPFIA1

• Liprin-alpha has LAR-independent functions in R7 photoreceptor axon targeting [10].
• ING4 and liprin alpha1 colocalized at lamellipodia in the vicinity of vinculin [2].
• The distribution of Pchlide-containing plastids in dark-grown lip1 mutant stem and root was similar to the distribution of chloroplasts in irradiated wild-type plants [11].

Associations of PPFIA1 with chemical compounds

• Here, we identified liprin alpha1/PPFIA1, a cytoplasmic protein necessary for focal adhesion formation and axon guidance, as a novel interacting protein with ING4 [2].
• LIP1 was also compared with Lipozyme RM IM as biocatalysts [12].

Physical interactions of PPFIA1

• Liprin phosphorylation regulates binding to LAR: evidence for liprin autophosphorylation [7].
• GIT1 is enriched in PSD fractions and forms a complex with liprin-alpha, GRIP, and AMPA receptors in brain [13].
• Here we report that liprin-alpha directly interacts with the ERC (ELKS-Rab6-interacting protein-CAST) family of proteins, members of which are known to bind RIMs, the active zone proteins that regulate neurotransmitter release [14].
• To better understand the structural basis of peptide recognition by a class II PDZ domain and PDZ-mediated multimerization, we determined the crystal structures of the GRIP1 PDZ6 domain alone and in complex with a synthetic C-terminal octapeptide of human liprin-alpha at resolutions of 1.5 and 1.8 A, respectively [15].

Regulatory relationships of PPFIA1

• Taken together, our results suggest that liprin autophosphorylation regulates its association with LAR [7].

Other interactions of PPFIA1

• This is the first report on comprehensive characterization of PPFIA4 belonging to the PPFIA family of kinesin-cargo linkers [16].
• Expression of dominant-negative constructs interfering with the GIT1-liprin-alpha interaction leads to a selective and marked reduction in the dendritic and surface clustering of AMPA receptors in cultured neurons [13].
• Liprin-alpha/SYD-2 is a family of multidomain proteins with four known isoforms [14].
• Recently, liprin-alpha proteins, which define active zone size and morphology, were found to associate with MALS/CASK, suggesting that this complex links the presynaptic release machinery to the active zone, thereby regulating neurotransmitter release [4].

References