Protein Amphipathic Helix Insertion: A Mechanism to Induce Membrane Fission

Abstract

Renard et al. (2018) suggested to classify membrane fission mechanisms into two main categories: active fission (with the direct consumption of cellular energy by nucleoside triphosphate hydrolysis) and passive fission (without the direct use of energy). Many membrane fission processes are dependent on the interaction of fission-inducing proteins with specific lipid molecules (see below). In some cases, passive fission might be energized indirectly, via the energy used in the synthesis of these lipid cofactors (Gopaldass et al., 2017). Moreover, membrane fission processes can be classified into two types: "normal topology fission" (membrane-enclosed compartments bud toward the cytosol) and "reverse topology fission" (membrane-enclosed compartments bud away from the cytosol) (

Sub-Nanometer Cryo-EM Density Map of the Human Heterodimeric Amino Acid Transporter 4F2hc-LAT2

“…Similar to this, the whole LAT2-HH would be correctly positioned to act as an amphipathic α-helix. Disruption of an amphipathic region may have an impact on protein/lipid interaction [ 34 , 35 ]. According to the 4F2hc-LAT2 hom model, S487 points toward the hydrophobic portion of the membrane as well as toward the protein moiety ( Figure 5 D) with no obvious hydrogen bonding partners nearby.…”

Membrane Curvature, Trans-Membrane Area Asymmetry, Budding, Fission and Organelle Geometry

“…An important aspect of membrane geometry in cells is the speed of the curvature delivery/extraction during fusion of membrane organelles, and the speed of alterations in their volume and surface area. For instance, the pulling tether is stable when it is formed slowly, and can be disrupted at higher speed [ 26 , 27 , 28 , 29 ]. Experiments with quick freezing of synapses, after their stimulation, demonstrated that lipid physics is responsible for these extremely fast formations of buds, on the presynaptic membrane after the fusion of synaptic vesicles with it [ 30 , 31 ].…”

“…For instance, proteins may also affect the local membrane properties as external factors. Membrane-bound proteins such as coatomer (COP) I, COPII, dynamin, clathrin/AP1, clathrin/AP2, AP3, AP4 (reviewed in [ 26 , 33 , 34 , 35 ]), with asymmetric distribution of mass across the bilayer, influence membrane bending in a nonspecific manner due to molecular crowding [ 36 ]. Shallow hydrophobic insertions and strongly curved protein scaffolds appear to be effective generators of the membrane curvature of intracellular organelles [ 37 ].…”

“…When insertion of proteins into the lipid bilayer occurs slowly, formation of membrane buds can be rather rare, because entropy-dependent diffusion of these proteins is faster than their insertion. Local augmentation of membrane curvature can occur due to sudden insertion or subsequent elimination of protein helices into the cytosolic leaflet [ 26 ]. The shape of the trans-membrane domains of proteins also affects the membrane curvature.…”

Chromogranin A preferential interaction with Golgi phosphatidic acid induces membrane deformation and contributes to secretory granule biogenesis

“…Altogether, our data show that CgA binds to specific species of PA which in turn could act as lipid cofactors 55 at the TGN to induce membrane remodeling and curvature in order to initiate secretory granule budding, concomitantly or prior to the recruitment of cytosolic proteins such as GOLPH3, 54 arfaptins, 56,57 the actomyosin 1b complex, 58 or the membrane‐associated myristoylated protein HID1, 59 but also small GTPase of the Arf family, 60 all of which are also essential actors in this fundamental biological process necessary for regulated secretion. Further studies are now needed to evaluate the connection of CgA/PA interaction with the additional machinery involved in secretory granule biogenesis, in living neuroendocrine cells, and the potential implication of this interaction in diseases related to hormone secretion deregulation.…”