1.C.118 The Mastoparin Peptide 1 (MPP1) Family

Mastoparin peptides form short (~14 aa) amphipathic peptdies in membranes that oligomerize to form channels in the membranes of target organism. Polybia-MP1 (MP1) is a bioactive host-defense peptide with known anticancer properties. Its activity is dependent on phosphatidylserine (PS) and phosphatidyl ethanolamine (PE) in the outer leaflet of cell membranes. PS and PE synergistically combine to enhance membrane poration by MP1, implying that the combined enrichment of both these lipids in the outer leaflet plays a role (Leite et al. 2015).

As mediators of innate immunity, neutrophils respond to chemoattractants by adopting a highly polarized morphology. Efficient chemotaxis requires the formation of one prominent pseudopod at the cell front characterized by actin polymerization, while local inhibition suppresses the formation of rear and lateral protrusions. This asymmetric control of signaling pathways is required for directional migration along a chemotactic gradient. The MAGUK protein p55/MPP1 is a mediator of the frontness signal required for neutrophil polarization (Quinn et al. 2009). Construction of a p55 knockout (p55−/−) mouse allowed demonstration that p55−/− neutrophils form multiple transient pseudopods upon chemotactic stimulation and do not migrate efficiently in vitro. Upon agonist stimulation, p55 is rapidly recruited to the leading edge of neutrophils in mice and humans. Total F-actin polymerization, along with Rac1 and RhoA activation, appear to be normal in p55−/− neutrophils. Phosphorylation of Akt is significantly decreased in p55−/− neutrophils upon chemotactic stimulation. The activity of immunoprecipitated phosphatidylinositol 3-kinase γ (PI3Kγ), responsible for chemoattractant-induced synthesis of PIP3 and Akt phosphorylation, is unperturbed in p55−/− neutrophils. Although the total amount of PIP3 is normal in p55−/− neutrophils, PIP3 is diffusely localized and forms punctate aggregates in activated p55−/− neutrophils, as compared to its accumulation at the leading edge membrane in the wild type neutrophils. Together, these results show that p55 is required for neutrophil polarization by regulating Akt phosphorylation through a mechanism that is independent of PI3Kγ activity (Quinn et al. 2009).


 

References:

Leite, N.B., A. Aufderhorst-Roberts, M.S. Palma, S.D. Connell, J.R. Neto, and P.A. Beales. (2015). PE and PS Lipids Synergistically Enhance Membrane Poration by a Peptide with Anticancer Properties. Biophys. J. 109: 936-947.

Quinn, B.J., E.J. Welch, A.C. Kim, M.A. Lokuta, A. Huttenlocher, A.A. Khan, S.M. Kuchay, and A.H. Chishti. (2009). Erythrocyte scaffolding protein p55/MPP1 functions as an essential regulator of neutrophil polarity. Proc. Natl. Acad. Sci. USA 106: 19842-19847.

Souza, B.M., M.A. Mendes, L.D. Santos, M.R. Marques, L.M. C├ęsar, R.N. Almeida, F.C. Pagnocca, K. Konno, and M.S. Palma. (2005). Structural and functional characterization of two novel peptide toxins isolated from the venom of the social wasp Polybia paulista. Peptides 26: 2157-2164.

Examples:

TC#NameOrganismal TypeExample
1.C.118.1.1

Polybia-Mastoparan-1 peptide, Polybia-MP1 of 14 aas.  Polybia-MP1 (MP1) is a bioactive host-defense peptide with known anticancer properties. Its activity is dependent on phosphatidylserine (PS) and phosphatidyl ethanolamine (PE) in the outer leaflet of cancer cell membranes (Leite et al. 2015). zit is a hemotactic peptide for polymorphonucleated leukocytes (PMNL), but causing no hemolysis to rat erythrocytes and no mast cell degranulation activity at physiological concentrations. It is also a potent antimicrobial peptide against Gram-positive bacteria B. subtilis CCT 2576 (MIC=4 µg/ml), and S. aureus ATCC 6538 (MIC=15 µg/ml) as well as Gram-negative bacteria E. coli ATCC 25922 (MIC=8 µg/ml) and P. aeruginosa ATCC 15422 (MIC=8 µg/ml) (Souza et al. 2005).

Polybia-MP1 of Polybia paulista (Neotropical social wasp) (Swarm-founding polistine wasp)

 
1.C.118.1.2

Mastoparan (MP) of 14 aas.  Potent antimicrobial peptide against both Gram-positive and Gram-negative bacteria. This hemolytic peptide shows potent histamine releasing activities on rat peritoneal mast cells.

MP of Protonectarina sylveirae (Brazilian wasp)