MPP1-based mechanism of resting state raft organization in the plasma membrane. Is it a general or specialized mechanism in erythroid cells?

Abstract

Biological membranes are organized in various microdomains, one of the best known being called membrane rafts. The major function of these is thought to organize signaling partners into functional complexes. An important protein found in membrane raft microdomains of erythroid and other blood cells is MPP1 (membrane palmitoylated protein 1)/p55. MPP1 (p55) belongs to the MAGUK (membrane-associated guanylate kinase homolog) family and it is a major target of palmitoylation in the red blood cells (RBCs) membrane. The wellknown function of this protein is to participate in formation of the junctional complex of the erythrocyte membrane skeleton. However, its function as a "raft organizer" is not well understood. In this review we focus on recent reports concerning MPP1 participation in membrane rafts organization in erythroid cells, including its role in signal transduction. Currently it is not known whether MPP1 could have a similar role in cell types other than erythroid lineage. We present also preliminary data regarding the expression level of MPP1 gene in several non-erythroid cell lines.

Structural organization of erythrocyte membrane microdomains and their relation with malaria susceptibility

“…Consistently, we detected skeletal proteins, including components of the junctional complex, mainly confined to cluster 4. This cluster also includes the junctional complex component Membrane Palmitoylated Protein 1 (MPP1/p55) that also functions as a raft organizer 15 . The raft-scaffolding protein Stomatin 16 and its interactors 17 are all grouped in the closely-related clusters 7 and 8 ( R = 0.75).…”

Not Just Another Scaffolding Protein Family: The Multifaceted MPPs

“…Recently, a member of the MPP family, MPP1, was shown to have another role in erythrocyte and erythroid cell membranes, besides its function as a scaffolding protein in the aforementioned ternary complex [10,38,57,135,136]. Studies on erythroid cells suggested that MPP1 may have a wider role in plasma membrane organization, in particular, in membrane raft formation [136].…”

“…Recently, a member of the MPP family, MPP1, was shown to have another role in erythrocyte and erythroid cell membranes, besides its function as a scaffolding protein in the aforementioned ternary complex [10,38,57,135,136]. Studies on erythroid cells suggested that MPP1 may have a wider role in plasma membrane organization, in particular, in membrane raft formation [136]. Using the erythrocyte progenitor cell line, HEL (human erythroleukemia), it turned out that the lack of palmitoylated MPP1 in the plasma membranes was the cause of these phenomena [10].…”

“…As flotillins are markers of membrane rafts, a question emerged on how MPP1 is connected to lateral membrane organization. One of the concepts regarding their formation involves interactions between raft-associated proteins [136,144,145]. This may be the mechanism explaining the role of MPP1-flotillin interaction in this process.…”

High-Level Expression of Palmitoylated MPP1 Recombinant Protein in Mammalian Cells

“…One of the most thoroughly examined members of this group, MPP1, was first described in red blood cells (RBCs) and is primarily known for its role in maintaining the proper shape of erythrocytes by participating in the formation of a ternary complex together with the 4.1R protein and glycophorin C [ 6 , 7 , 8 ]. Importantly, our previous studies demonstrated the key role of MPP1 in the lateral organization of the erythroid cell membrane [ 9 , 10 , 11 , 12 ]. Experiments performed on the human erythroleukemia cell line (HEL), which are erythrocyte progenitor cells, showed that silencing MPP1 expression or the inhibition of its palmitoylation significantly reduced the order parameters of both PM or PM-derived vesicles in comparison to control cells [ 9 , 13 ].…”