Phosphatidylinositol 4,5-bisphosphate  (Synonyms: L-alpha-Phosphatidylinositol-4,5-bisphosphate; (PtdIns)-(4,5)-P2)

Phosphatidylinositol 4,5-bisphosphate (L-alpha-Phosphatidylinositol-4,5-bisphosphate) is a plasma membrane lipid that is enriched in the cytoplasmic leaflet of the plasma membrane. Phosphatidylinositol 4,5-bisphosphate serves as a substrate for phospholipase C and class I PI3K, generating diacylglycerol, inositol (1,4,5)-trisphosphate, and phosphatidylinositol (3,4,5)-trisphosphate. Phosphatidylinositol 4,5-bisphosphate contributes to lamellipodial protrusion, directional cell migration, focal adhesion lipid generation, and trafficking of the GABA_A receptor. Phosphatidylinositol 4,5-bisphosphate can be used in research related to acute lung injury and pulmonary edema^[1][2][3].

Phosphatidylinositol 4,5-bisphosphate (L-alpha-Phosphatidylinositol-4,5-bisphosphate) (10-25 μM, endogenous levels; 200-400 s, 250 s) and its water-soluble analog diC8-PI(4,5)P₂ maintain the conductive state of wild-type mouse ANO1 channels in HEK cells by preventing Ca²⁺-induced inactivation and rescuing channel activity after PI(4,5)P₂ depletion^[2].
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) (10 μM) binds to specific residues in multiple sites on mouse ANO1 channels to regulate channel gating and prevent Ca²⁺-induced inactivation, with mutations in these sites eliminating or reducing PI(4,5)P₂ sensitivity^[2].
Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P₂) modulates the conformation of mouse ANO1 channels by inducing TM6 rotation, which prevents Ca²⁺-induced pore collapse and maintains the conductive channel state^[2].
Phosphatidylinositol 4,5-bisphosphate constitutes 1-2 mol^% of total mammalian plasma membrane lipid, with a specific stearic acid-arachidonic acid acyl chain profile, and is the most abundant cellular phosphoinositide^[3].
Phosphatidylinositol 4,5-bisphosphate acts as a substrate for mammalian PLC isoforms, whose hydrolysis produces the second messengers IP₃ and DAG to drive downstream Ca²⁺ and PKC signaling^[3].
Phosphatidylinositol 4,5-bisphosphate dynamically regulates mammalian actin cytoskeleton dynamics by modulating the activity and localization of actin-binding proteins, including ERM proteins, cofilin, and N-WASP, with PLC-mediated PI(4,5)P₂ depletion driving actin disassembly and cell migration in carcinoma cells^[3].
Phosphatidylinositol 4,5-bisphosphate is essential for multiple steps of mammalian clathrin-mediated endocytosis, including AP2 activation, clathrin recruitment, membrane deformation, dynamin-mediated scission, and regulation of vesicle uncoating via localized production and degradation^[3].
Phosphatidylinositol 4,5-bisphosphate directly regulates the activity and localization of multiple mammalian plasma membrane ion channels, maintaining Kir and KCNQ channels in an open state, inhibiting TRPV4 channels, and contributing to GABA_A receptor membrane localization, with PLC-mediated PI(4,5)P₂ depletion dynamically altering channel activity^[3].
Phosphatidylinositol 4,5-bisphosphate forms nanoscale clusters (~65-73 nm) in the mammalian plasma membrane, with a portion bound to cytoskeletal proteins, and its local enrichment is regulated by lipid raft trapping, protein sequestration, and localized synthesis^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Phosphatidylinositol 4,5-bisphosphate (L-alpha-Phosphatidylinositol-4,5-bisphosphate) (150-750 μM; intrapulmonary instillation; single dose) dose-dependently stimulates alveolar fluid clearance in normal male and female Sprague Dawley rats via an amiloride/ENaC-dependent pathway, with an EC₅₀ of 170 μM in males and ~93% increased clearance at 300 μM in both genders, and membrane residency is required for full stimulatory activity^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1047.09

C₄₇H₈₅O₁₉P₃

245126-95-8

O=P(O)(O)O[C@H]1[C@@H]([C@H]([C@@H](O)[C@@H](OP(OC[C@@H](COC(CCCCCCCCCCCCCCCCC)=O)OC(CCC/C=C\C/C=C\C/C=C\C/C=C\CCCCC)=O)(O)=O)[C@@H]1O)O)OP(O)(O)=O

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Kooijman EE, et al. Phosphatidylinositol 4,5-bisphosphate stimulates alveolar epithelial fluid clearance in male and female adult rats. Am J Physiol Lung Cell Mol Physiol. 2011;301(5):L804-L811.  [Content Brief]

  [2]. Arreola J, et al. Wasted TMEM16A channels are rescued by phosphatidylinositol 4,5-bisphosphate. Cell Calcium. 2019;84:102103.  [Content Brief]

  [3]. Katan M, et al. Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane. Essays Biochem. 2020;64(3):513-531.  [Content Brief]