Deciphering the BAR code of membrane modulators

Abstract

The BAR domain is the eponymous domain of the “BAR-domain protein superfamily”, a large and diverse set of mostly multi-domain proteins that play eminent roles at the membrane cytoskeleton interface. BAR domain homodimers are the functional units that peripherally associate with lipid membranes and are involved in membrane sculpting activities. Differences in their intrinsic curvatures and lipid-binding properties account for a large variety in membrane modulating properties. Membrane activities of BAR domains are further modified and regulated by intramolecular or inter-subunit domains, by intermolecular protein interactions, and by posttranslational modifications. Rather than providing detailed cell biological information on single members of this superfamily, this review focuses on biochemical, biophysical, and structural aspects and on recent findings that paradigmatically promote our understanding of processes driven and modulated by BAR domains.

Receptor‐Free Signaling at Curved Cellular Membranes

“…Here, liposomes prepared from lipid extracts (e.g., brain, liver) or model membranes with predetermined lipid composition are used to reconstitute bilayers devoid of protein constituents. [81] Specifically, liposomes of varied curvatures are obtained by extruding them through filters of predefined pore size, followed by incubation with purified proteins. [81] Specifically, liposomes of varied curvatures are obtained by extruding them through filters of predefined pore size, followed by incubation with purified proteins.…”

“…However, considering the continuous changes in curvature and lipid composition in cellular membranes, [79,80] such data should be interpreted with great caution. Indeed, data from individual www.advancedsciencenews.com www.bioessays-journal.com labs on specific proteins/membrane interactions present at times contradicting results (reviewed in Salzer et al [81] ). To illustrate this point, let us have a closer look at protein recruitment to membrane tethers (Figure 2A), which can be pulled via OT.…”

“…[95] Such in vitro approaches are powerful, as they allow analysis of protein/ membrane interactions in a quantitative and reproducible manner. [81] Specifically, liposomes of varied curvatures are obtained by extruding them through filters of predefined pore size, followed by incubation with purified proteins. The resulting protein-membrane interactions are then either determined via transmission electron microscopy (TEM), co-sedimentation, or cofloatation assays.…”

RNAi screen inTriboliumreveals involvement of F-BAR proteins in myoblast fusion and visceral muscle morphogenesis in insects

“…A new gene with a 'thin muscle' phenotype upon RNAi not previously implicated in myoblast fusion was TC013784, the ortholog of Drosophila CG42388, which subsequent to our screen was named after its mammalian ortholog, Nostrin (Nost) (Zimmermann et al 2002;Zobel et al 2015). The encoded Nostrin is a member of the family of F-BAR proteins that are known to regulate membrane curvature and actin turnover in a variety of contexts (Fricke et al 2010;Liu et al 2015;Salzer et al 2017). The phenotype was present with similar strength upon injections of different amounts of the TC013784 iB dsRNA and of a non-overlapping Tc-Nost dsRNA into pig-19, as well as upon iB dsRNA injection into the SB strain of Tribolium castaneum ( Fig.…”

“…This gene encodes a protein with an F-BAR domain within its N-terminal half and an SH3 domain at its C-terminus. F-BAR proteins associate as curved homo-dimers with the inner face of the plasma membrane via binding to phospholipids and regulate membrane curvature as well as actin polymerization in various contexts (Roberts-Galbraith and Gould 2010;Liu et al 2015;Salzer et al 2017).…”