Cellular and molecular mechanisms underlying plasma membrane functionality and integrity

Abstract

The plasma membrane not only protects the cell from the extracellular environment, acting as a selective barrier, but also regulates cellular events that originate at the cell surface, playing a key role in various biological processes that are essential for the preservation of cell homeostasis. Therefore, elucidation of the mechanisms involved in the maintenance of plasma membrane integrity and functionality is of utmost importance. Cells have developed mechanisms to ensure the quality of proteins that inhabit the cell surface, as well as strategies to cope with injuries inflicted to the plasma membrane. Defects in these mechanisms can lead to the development or onset of several diseases. Despite the importance of these processes, a comprehensive and holistic perspective of plasma membrane quality control is still lacking. To tackle this gap, in this Review, we provide a thorough overview of the mechanisms underlying the identification and targeting of membrane proteins that are to be removed from the cell surface, as well as the membrane repair mechanisms triggered in both physiological and pathological conditions. A better understanding of the mechanisms underlying protein quality control at the plasma membrane can reveal promising and unanticipated targets for the development of innovative therapeutic approaches.

Volleying plasma membrane proteins from birth to death: Role of J-domain proteins

“…Anchored by Farnesylation at C-terminal CAAX domain (Caplan et al, 1992) Emr, 2021; Vasconcelos-Cardoso et al, 2022). At each of these steps, PM proteins must pass the "fit to move forward" test.…”

“…Cells are extremely sensitive to conformationally compromised PM proteins, and often this leads to loss of cell integrity or death ( Zhao et al, 2013 ; Juarez-Navarro et al, 2020 ). To circumvent this, cells employ efficient, multi-layered cellular protein quality control (PQC) machineries which act as stringent checkpoints to tightly regulate the synthesis, folding, and degradation of PM proteins (Reviewed in ( Apaja et al, 2010 ; Okiyoneda et al, 2011 ; Babst, 2014 ; MacGurn, 2014 ; Sardana and Emr, 2021 ; Vasconcelos-Cardoso et al, 2022 ). At each of these steps, PM proteins must pass the “fit to move forward” test.…”

Charge-regulated fluorescent anchors enable high-fidelity tracking of plasma membrane dynamics during biological events

“…The plasma membrane, as the defender of the most basic unit of life activities, performs important functions such as maintaining cell viability, ensuring cell integrity, regulating the transport of substances across the membrane and participating in signal transduction. 1 Many important biological events, such as cell plasma membrane damage and repair, cell fusion, cytokinesis and proliferation, etc. , are usually accompanied by significant changes in the morphology and dynamics of the plasma membrane.…”

Rational Design of Self-Reporting Photosensitizers for Cell Membrane-Targeted Photodynamic Therapy

“…Recent years have witnessed proliferation of PSs with intriguing properties, including enhanced 1 O 2 quantum yield with minimal dark toxicity, , organelle-targeting ability, − and red to near-infrared (NIR) absorption . Among the cellular organelles, cell membrane plays a crucial role in maintaining cellular integrity and communication, and membrane disruption has been validated as an effective method to induce cell death. , Till now, dozens of membrane-targeted PSs have been reported ,− and exceptional therapeutic results have been achieved. Nevertheless, most of them still suffer from short absorption wavelength, which hinders their clinical application.…”