Alternative titles; symbols
HGNC Approved Gene Symbol: PPFIA2
Cytogenetic location: 12q21.31 Genomic coordinates (GRCh38) : 12:81,257,975-81,759,350 (from NCBI)
PPFIA2, or liprin-alpha-2, belongs to the liprin-alpha gene family (Serra-Pages et al., 1998). See liprin-alpha-1 (LIP1, or PPFIA1; 611054) for background on liprins.
Members of the LAR (179590) family are transmembrane protein-tyrosine phosphatases (PTPases). The LIP1 protein had been shown to bind to the LAR membrane-distal D2 PTPase domain. Serra-Pages et al. (1998) identified a family of genes encoding LIP1-related proteins, or liprins. The predicted 1,257-amino acid liprin-alpha-2 protein is 72% identical to LIP1, which the authors renamed liprin-alpha-1. Northern blot analysis revealed that the liprin-alpha-2 gene is expressed as a 6.5-kb mRNA only in brain.
Gross (2022) mapped the PPFIA2 gene to chromosome 12q21.31 based on an alignment of the PPFIA2 sequence (GenBank BC143485) with the genomic sequence (GRCh38).
Using immunofluorescence studies in mammalian cells, Serra-Pages et al. (1998) showed that LAR and liprin-alpha-2 colocalize at the cell surface. The LAR membrane-distal D2 PTPase domain was required for this colocalization and LAR clustering. Serra-Pages et al. (1998) proposed that liprins are multivalent proteins that form complex structures that act as scaffolds for the recruitment and anchoring of LAR family PTPases.
Using a mass spectrometry approach, Stucchi et al. (2018) identified TANC2 (615047), liprin-alpha-2, and the calcium-binding protein calmodulin (see 114180) as direct binding partners of KIF1A (601255), the primary motor protein for synaptic vesicles (SVs) and dense core vesicles (DCVs). Analysis with rat hippocampal neurons revealed that calcium enhanced Kif1a binding to DCVs and increased vesicle motility by acting through calmodulin. Tanc2 and liprin-alpha-2 were enriched in dendritic spines but were not part of the Kif1a cargo complex. Instead, they acted as postsynaptic density scaffolds to stop and capture Kif1a-bound DCVs upon dendritic spine entry. Knockdown experiments showed that depletion of Tanc2, Kif1a, or liprin-alpha-2 affected rat dendritic spine density and morphology.
Gross, M. B. Personal Communication. Baltimore, Md. 9/2/2022.
Serra-Pages, C., Medley, Q. G., Tang, M., Hart, A., Streuli, M. Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. J. Biol. Chem. 273: 15611-15620, 1998. [PubMed: 9624153] [Full Text: https://doi.org/10.1074/jbc.273.25.15611]
Stucchi, R., Plucinska, G., Hummel, J. J. A., Zahavi, E. E., Guerra San Juan, I., Klykov, O., Scheltema, R. A., Maarten Altelaar, A. F., Hoogenraad, C. C. Regulation of KIF1A-driven dense core vesicle transport: Ca(2+)/CaM controls DCV binding and liprin-alpha/TANC2 recruits DCVs to postsynaptic sites. Cell Rep. 24: 685-700, 2018. [PubMed: 30021165] [Full Text: https://doi.org/10.1016/j.celrep.2018.06.071]