Lipid raft–associated stomatin enhances cell fusion

Abstract

Membrane fusions that occur during vesicle transport, virus infection, and tissue development, involve receptors that mediate membrane contact and initiate fusion and effectors that execute membrane reorganization and fusion pore formation. Some of these fusogenic receptors/effectors are preferentially recruited to lipid raft membrane microdomains. Therefore, major constituents of lipid rafts, such as stomatin, may be involved in the regulation of cell-cell fusion. Stomatin produced in cells can be released to the extracellular environment, either through protein refolding to pass across lipid bilayer or through exosome trafficking. We report that cells expressing more stomatin or exposed to exogenous stomatin are more prone to undergoing cell fusion. During osteoclastogenesis, depletion of stomatin inhibited cell fusion but had little effect on tartrate-resistant acid phosphatase production. Moreover, in stomatin transgenic mice, increased cell fusion leading to enhanced bone resorption and subsequent osteoporosis were observed. With its unique molecular topology, stomatin forms molecular assembly within lipid rafts or on the appositional plasma membranes, and promotes membrane fusion by modulating fusogenic protein engagement.-Lee, J.-H., Hsieh, C.-F., Liu, H.-W., Chen, C.-Y., Wu, S.-C., Chen, T.-W., Hsu, C.-S., Liao, Y.-H., Yang, C.-Y., Shyu, J.-F., Fischer, W. B., Lin, C.-H. Lipid raft-associated stomatin enhances cell fusion.

Extracellular membrane vesicles in the three domains of life and beyond

“…Interestingly, stomatin is known to be a major protein in vesicular lipid rafts, and despite being first detected in Eukaryotes, was later identified in both Bacteria and Archaea, suggesting some degree of conserved membrane dynamics across the three domains (Tavernarakis, Driscoll and Kyrpides 1999; Lee et al. 2017). For an exhaustive review on cargo selection in eukaryotic EVs, see Villarroya-Beltri et al.…”

“…Among proteins usually found in EVs, the only possible universal proteins could be proteins of the SPFH superfamily that are known to facilitate membrane curvature and cell fusion (Lee et al. 2017) and have been involved in the production of some eukaryotic EVs (Hinderhofer et al. 2009).…”

Structure-function analysis of human stomatin: A mutation study

“…Similarly, in neutrophils, stomatin is associated with azurophil granules, but also other specific granules [13], and is likewise relocated to the plasma membrane upon activation [1]. Stomatin is also expressed in placental cells, where it may play an important role in trophoblast differentiation [14], and in bone, where it promotes osteoclastogenesis [15]. Trafficking of stomatin to the plasma membrane appears to follow the Golgi-pathway [16], while endocytosis most probably follows a clathrin-independent endocytosis pathway similar to caveolin-1 [17] and flotillins [18].…”

Function of Platelet Glycosphingolipid Microdomains/Lipid Rafts

“…Lipid raft-associated stomatin enhances cell fusion. With its unique molecular topology, stomatin forms molecular assemblies within lipid rafts, and promotes membrane fusion by modulating fusogenic protein engagement [104]. During platelet activation, the α-granular membrane undergoes fusion with the platelet plasma membrane and granular secretion.…”