Plasma Membrane Markers

What is the Plasma Membrane?

The plasma membrane is a selectively permeable lipid bilayer that separates the cytoplasm and intracellular components from the extracellular environment of a cell. It is a highly dynamic structure comprised of lipids and proteins, responsive to extracellular signals, like cytokines, hormones, and ions, resulting in intracellular signaling cascades. Movement of substances across the plasma membrane occurs via passive or active transport, the latter of which requires the expenditure of energy. Smaller molecules can cross the cell membrane by passive diffusion whereas larger, more polar molecules generally require active transporter-mediated entry. The plasma membrane also serves as the attachment point for the intracellular cytoskeleton, which helps to determine cell shape and motility.

Cartoon graphic depicting the lipid bilayer and various proteins that constitute the plasma membrane.

Illustration of protein organization within the lipid bilayer to form the structure of the plasma membrane. The membrane forms a semipermeable barrier between the extracellular and intracellular compartments and provides interaction points with the cytoskeleton.

Plasma Membrane Markers and Applications

Plasma Membrane Lipids

The phospholipid bilayer consists of two layers of phospholipids with the hydrophilic heads facing the extra- and intracellular environments and hydrophobic tails in the middle. In addition to phospholipids (e.g. phosphatidylserine (PtdSer), phosphatidylcholine (PtdCho)), other lipids, such as sphingolipids (e.g. sphingomyelin (SM)) and cholesterol are abundant in the plasma membrane. Lipids are essential for cell membrane energy storage, compartmentalization, membrane fluidity, and signaling.

View Fluorescent Lipid Probes & Cell Membrane Stains from Tocris

Plasma Membrane Proteins

Common types of plasma membrane proteins include pumps and transporters, enzymes, receptors, and anchors. For example, G-protein coupled receptors (GPCRs) are a large family of receptors that convert extracellular messages into intracellular signaling cascades. The GPCR family of proteins includes important cytokine and chemokine receptors responsible for cell trafficking, like CCR7 and CXCR4. Sodium Potassium ATPase and Pma1 are two common membrane ATPase pumps that have traditionally served as general plasma membrane markers.

Plasma membrane proteins also serve as drug candidate targets for the many pathologies associated with dysfunctional membrane proteins. Potential therapeutics can affect the protein function by blocking transport or inhibiting ligand binding, for example, resulting in cellular signaling modifications.

Antibodies to markers for the plasma membrane can be used in a wide range of applications including immunocytochemistry (ICC)/immunofluorescence (IF), immunohistochemistry (IHC), western blot, ELISA, flow cytometry, and immunoprecipitation (IP).

Immunocytochemistry/Immunofluorescence image of choroidal epithelial cells showing Na+K+ ATPase Alpha 1 (red) and ABCC1 (green) antibody staining, with nuclear stain (blue), highlighting a single cell view (left) and z-stack view (right).

Immunofluorescent image depicting the cellular model of the blood-cerebrospinal fluid (CSF) barrier. Choroidal epithelial cells were stained with Mouse Anti-Sodium Potassium ATPase Alpha 1 Monoclonal Antibody (Catalog #NB300-146) (red) and Rabbit Anti-ABCC1 Polyclonal Antibody (green), highlighting the respective apical and basolateral membrane localization. (Left) Close up image of a single cell showing the polarity of distribution between Na+K+ ATPase and ABCC1, and the nuclei (blue). (Right) Confocal analysis of cells in z-stack. Arrows point to the lateral cellular membranes, whereas the arrowheads emphasize the basal labeling of ABCC1. Image collected and cropped by CiteAb from the following publication (//, licensed under a CC-BY 4.0 license.

Common Plasma Membrane Markers and Function:


Functional Role of Protein

Aquaporin-2 Plasma membrane protein channel involved in water transport in the renal collecting duct.
Caveolin-1 Cholesterol-binding integral protein that is a major component of invaginations in the plasma membrane called caveolae which function in lipid metabolism.
CD40 Glycoprotein expressed on the surface of B cells and antigen presenting cells (APCs) with a role in B lymphocyte survival and differentiation.
CD40L Single-pass type II membrane protein typically expressed by CD4+ T cells that binds the CD40 protein.
CD98 Type II transmembrane glycoprotein that functions in amino acid transport and integrin signaling.
E-Cadherin Epithelial cadherin that is a cell-cell glycoprotein that is essential in multiple cellular processes including polarity, migration, and tissue integrity.
ENPP-1 Plasma membrane protein that helps breakdown ATP.
Glut1 12-pass membrane spanning integral glycoprotein responsible for the transport of glucose across membranes.
N-Cadherin Neuronal cadherin is a calcium-dependent transmembrane glycoprotein with a role in cell-cell adhesion.
Pan Cadherin Classical cadherin that is a single chain glycoprotein receptor responsible for mediating calcium dependent cell-cell adhesion. Pan Cadherin recognizes all cadherin family members including E-Cadherin and N-Cadherin.
Pma1 Plasma membrane H+-ATPase that pumps protons out of the cell, regulating membrane potential and cytoplasmic pH levels.
PMCA Calcium (Ca2+) pump of the plasma membrane that pumps cytosolic Ca2+ out of the cell.
Sodium Potassium ATPases: Alpha 1, Alpha 2, Alpha 3, Alpha 4, Beta 1 An enzyme that acts as a plasma membrane pump responsible for maintaining resting potential within the cell. Uses ATP to transport sodium (Na+) and potassium (K+) ions across the plasma membrane to maintain a low intracellular Na+ concentration and high K+ concentration.
Tight Junction Protein 2 (TJP2)/ZO-2 Scaffolding protein that organizes membrane receptors and tight junction proteins to the actin cytoskeleton and helps define apical and basolateral domains of the plasma membrane.
TJP3/ZO-3 Closely related to TJP2/ZO-2. A scaffolding protein linking transmembrane proteins and adhesion molecules to the actin cytoskeleton.

Note: The markers listed in the table is not an exhaustive list of all plasma membrane markers.

View Plasma Membrane Marker Reagents

Immunocytochemistry/Immunofluorescence image of frozen section of mouse skin showing E-Cadherin expression following secondary antibody staining (red) and the nuclei (blue), with E-cadherin localized to keratinocytes in the plasma membrane. Immunohistochemistry image of human kidney tissue probed with anti-CD98 monoclonal antibody showing high membrane staining.

Perfusion fixed frozen sections of mouse skin showing E-Cadherin expression by probing with Goat Anti-E Cadherin Polyclonal Antibody (Catalog #AF748) followed by staining with NorthernLights™ 557-conjugated Anti-Goat IgG Secondary Antibody (Catalog #NL001) (red) and counterstaining nuclei with DAPI (blue). E-Cadherin staining was localized to keratinocytes in the plasma membranes.

Immunohistochemical analysis of CD98 expression in formalin-fixed paraffin-embedded tissue section of human kidney using Mouse Anti-CD98 Monoclonal Antibody (1C11.7E3) (Catalog #NBP2-36491). The CD98 antibody showed distinct membranous staining with weaker cytoplasmic signal. Staining was localized to the tubular epithelial cells of the kidney and was absent in the Bowman's capsules.

Western blot of retinal lysates from Tg40 PrP and PrP-/- knockout mice treated with ferric ammonium citrate (FAC) and probed with Anti-Glut1 Antibody showing upregulation of Glut1 in PrP-/- samples compared to Tg40 PrP samples as well as FAC treatment-induced downregulation of Glut1 in Tg40 PrP samples.

Biological Strategies Validation. Western blot analysis showing the effect of iron overloading using ferric ammonium citrate (FAC) on glucose transporter Glut1 expression in the neuroretina lysates from prion protein (PrP) knockout (PrP-/-) mice and Tg40 PrP mice. Retinal lysates probed with Rabbit Anti-Glut1 Polyclonal Antibody (Catalog #NB110-39113) display upregulation of Glut1 in PrP-/- samples compared to Tg40 PrP samples (lanes 1 & 3). FAC treatment results in Glut1 downregulation in Tg40 PrP samples relative to untreated controls but has a negligible effect in the similarly treated PrP-/- samples (lanes 2 & 4). Image collected and cropped by CiteAb from the following publication ( licensed under a CC-BY 4.0 license.

Plasma Membrane Damage, Repair, and Role in Disease Pathology

Plasma Membrane Damage and Repair

Insults to the plasma membrane can result from a variety of different causes including mechanical, chemical, microbial, immune, or intracellular mechanisms. A physical breach or chemical disruption can induce plasma membrane damage and leave the cell susceptible to further injury. Chemical damage through radiation or reactive oxygen species (ROS) can make mechanical stress like nanoruptures and pore formation more likely.

Many cell death pathways such as apoptosis, necroptosis, and ferroptisis are characterized, in part, by plasma membrane damage. One of the earliest signs of apoptosis is transition of PtdSer from the inner membrane to the outer membrane. Novus Biologicals’ Polarity Sensitive Indicator of Viability and Apoptosis (pSIVA) contains an Annexin-based probe to detect apoptosis by PtdSer externalization, both irreversible and transient. Our pSIVA Apoptosis Detection Kits are suitable for multiple applications including flow cytometry and ICC/IF.

Untreated, 1hr- and 2hr-Staurosporine treated Jurkat cells stained with the pSIVA Kit showing increased percentage of positive cells following treatment via flow cytometry analysis, indicating movement from healthy to dying cells.

Flow Cytometry analysis showing either untreated or Staurosporine treated Jurkat cells stained with Polarity Sensitive Indicator of Viability Apoptosis (pSIVA) Kit [IANBD] (Catalog #NBP2-29611). Results show increasing positive population staining percentage with the pSIVA Kit in the Staurosporine-treated cells, indicative of cell death.

The plasma membrane follows four stages of repair after a physical breach:

  1. Sealing off a physical breach via various mechanisms such as exocytosis, endocytosis, patching, plugging, contraction, constriction, and scission

  2. Removal of harmful materials

  3. Replacement of damaged cellular components

  4. Remodeling or adaptive responses

The Role of the Plasma Membrane in Disease Pathogenesis

Defective plasma membrane repair pathway and the inability to restore plasma membrane integrity can cause or exacerbate the pathogenesis of a variety of diseases such as inflammatory bowel disease, neurodegenerative disorders, and muscular dystrophies (MDs). Muscular dystrophies, for example, are often characterized by increased membrane permeability, resulting in degradation of the muscle and loss of function. Similarly, plasma membrane integrity is lost during Alzheimer’s disease and Parkinson’s disease pathogenesis, as the disease-associated proteins form aggregates.

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