Target type: biologicalprocess
The specification and formation of the apicobasal polarity of an epithelial cell. [GOC:ascb_2009, GOC:bf, GOC:dph, GOC:tb]
The establishment of epithelial cell apical/basal polarity is a fundamental process that underlies the formation and function of epithelial tissues. It involves the coordinated and dynamic regulation of a complex network of molecular machinery, including proteins, lipids, and cytoskeletal elements. Here's a detailed description of the biological process:
**1. Intrinsic Polarity Cues:**
- The intrinsic polarity of epithelial cells is determined by factors like cell-cell junctions and the distribution of membrane-associated proteins.
- **Tight junctions (TJs)** act as a barrier between the apical and basolateral domains, restricting the movement of proteins and lipids. They are crucial for establishing and maintaining the apical-basal polarity.
- **Adherens junctions (AJs)** connect epithelial cells to each other, providing structural support and playing a role in cell-cell communication. They are also involved in the polarization of the cytoskeleton.
- **Apical proteins**, such as occludin, claudin, and ZO proteins, are concentrated at the apical membrane and contribute to the formation and maintenance of tight junctions.
- **Basolateral proteins**, such as E-cadherin, β-catenin, and α-catenin, are localized to the basolateral membrane and play a role in cell-cell adhesion and signal transduction.
**2. Extrinsic Polarity Cues:**
- **Extracellular matrix (ECM)** cues, such as laminin and collagen, interact with basolateral receptors on epithelial cells, influencing their polarization.
- **Growth factors and signaling molecules**, secreted from neighboring cells or the ECM, can also modulate the establishment of apical-basal polarity.
- **Mechanical forces**, such as stretching or compression, can influence cell shape and contribute to polarization.
**3. Trafficking and Sorting Mechanisms:**
- **Vesicular transport**, mediated by specialized protein complexes, plays a crucial role in delivering proteins and lipids to the correct membrane domains.
- **Exocytosis**, the process of releasing intracellular vesicles to the cell surface, is essential for apical and basolateral membrane growth and polarization.
- **Endocytosis**, the internalization of membrane components, allows for the recycling and degradation of proteins and lipids, maintaining the integrity of the polarized cell.
**4. Cytoskeletal Organization:**
- The **actin cytoskeleton** is involved in the formation and maintenance of cell junctions, as well as the transport of vesicles and proteins.
- **Microtubules**, another component of the cytoskeleton, play a role in the transport of organelles and the alignment of the apical-basal axis.
**5. Regulation of Gene Expression:**
- The establishment of epithelial cell polarity involves the coordinated regulation of gene expression, leading to the synthesis of specific proteins and lipids that are required for polarization.
- Transcription factors, such as PAR proteins and Cdc42, play crucial roles in regulating gene expression and directing the differentiation of epithelial cells.
**6. Dynamic and Adaptive Process:**
- Epithelial cell polarity is a dynamic and adaptive process, constantly responding to changes in the cellular environment.
- During development, cell migration, or tissue repair, epithelial cells can re-polarize to adapt to new conditions.
- This dynamic nature of epithelial cell polarity is essential for tissue homeostasis and function.
In summary, the establishment of epithelial cell apical/basal polarity is a complex and multifaceted process involving intricate interactions between intrinsic and extrinsic factors, trafficking and sorting mechanisms, cytoskeletal organization, and gene expression regulation. This process is essential for the formation and function of epithelial tissues, which play crucial roles in various biological processes, including barrier formation, nutrient absorption, and secretion.'
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Protein | Definition | Taxonomy |
---|---|---|
Transforming protein RhoA | A GTP-binding protein RhoA that is encoded in the genome of human. [PRO:CNA, UniProtKB:P61586] | Homo sapiens (human) |
Cell division control protein 42 homolog | A cell division control protein 42 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P60953] | Homo sapiens (human) |
Ezrin | An ezrin that is encoded in the genome of human. [PRO:CNA, UniProtKB:P15311] | Homo sapiens (human) |
Na(+)/H(+) exchange regulatory cofactor NHE-RF1 | A Na(+)/H(+) exchange regulatory cofactor NHE-RF1 that is encoded in the genome of human. [PRO:CNA, UniProtKB:O14745] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
fasudil | fasudil : An isoquinoline substituted by a (1,4-diazepan-1-yl)sulfonyl group at position 5. It is a Rho-kinase inhibitor and its hydrochloride hydrate form is approved for the treatment of cerebral vasospasm and cerebral ischemia. fasudil: intracellular calcium antagonist; structure in first source | isoquinolines; N-sulfonyldiazepane | antihypertensive agent; calcium channel blocker; EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor; geroprotector; neuroprotective agent; nootropic agent; vasodilator agent |
ketorolac | 5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid : A member of the class of pyrrolizines that is 2,3-dihydro-1H-pyrrolizine which is substituted at positions 1 and 5 by carboxy and benzoyl groups, respectively. ketorolac : A racemate comprising equimolar amounts of (R)-(+)- and (S)-(-)-5-benzoyl-2,3-dihydro-1H-pyrrolizine-1-carboxylic acid. While only the (S)-(-) enantiomer is a COX1 and COX2 inhibitor, the (R)-(+) enantiomer exhibits potent analgesic activity. A non-steroidal anti-inflammatory drug, ketorolac is mainly used (generally as the tromethamine salt) for its potent analgesic properties in the short-term management of post-operative pain, and in eye drops to relieve the ocular itching associated with seasonal allergic conjunctivitis. It was withdrawn from the market in many countries in 1993 following association with haemorrhage and renal failure. Ketorolac: A pyrrolizine carboxylic acid derivative structurally related to INDOMETHACIN. It is an NSAID and is used principally for its analgesic activity. (From Martindale The Extra Pharmacopoeia, 31st ed) | amino acid; aromatic ketone; monocarboxylic acid; pyrrolizines; racemate | analgesic; cyclooxygenase 1 inhibitor; cyclooxygenase 2 inhibitor; non-steroidal anti-inflammatory drug |
sanguinarine chloride | |||
chelerythrine chloride | |||
nsc668394 | |||
2-[[benzamido(sulfanylidene)methyl]amino]-5,5-dimethyl-4,7-dihydrothieno[2,3-c]pyran-3-carboxylic acid | CID1067700: a pan-GTPase inhibitor; structure in first source | thienopyran | |
fh535 | FH535: inhibits Wnt signaling | sulfonamide | |
y 27632, dihydrochloride, (4(r)-trans)-isomer | |||
secramine a | secramine A: inhibits VSVG transport from the Golgi to the plasma membrane; also inhibits Cdc42-dependent cell functions; structure in first source | ||
ccg-203971 |