Pard3 is a protein that plays a role in intricate cellular processes. It orchestrates cellular functions contributing to overall health and development. Understanding Pard3’s function offers insights into the fundamental mechanisms that govern cellular order. Its widespread presence across cell types highlights its broad influence in maintaining healthy tissues and organs.
Defining Pard3
Pard3, or Partitioning defective 3 homolog, is a protein encoded by the PARD3 gene. It functions as a scaffolding protein, organizing other proteins to facilitate cellular activities. It forms large complexes, notably with PAR6 and atypical protein kinase C (aPKC), creating the PAR polarity complex.
Pard3 is found at various cellular locations, including the cell membrane at tight junctions, which seal cells together. It can also be found in the cytoplasm. It is expressed in a wide range of human tissues and cell types, including those in the kidney, lung, liver, nervous system, and skin.
Pard3’s Blueprint for Cellular Order
Pard3 plays a central role in establishing and maintaining cell polarity, the internal organization of a cell with distinct regions and functions. Cells have a defined “top” (apical) and “bottom” (basolateral) or “front” and “back,” allowing them to perform specialized tasks. In epithelial cells, for instance, Pard3 localizes at tight junctions, forming a boundary between the apical and basolateral domains.
Cell polarity is important for many fundamental biological processes. It directs proper cell division, ensuring correct distribution of cellular components to daughter cells. In neural stem cells, for example, apically located Pard3 is involved in signaling pathways that determine cell fate during asymmetric cell division. Pard3 also influences cell migration, guiding cells to move in the correct direction within tissues. Pard3 can interact with proteins like FAK and PI3-kinase, enhancing their activities for polarized cell migration.
Pard3 acts as a central organizer by interacting with other proteins to create this cellular blueprint. It forms a complex with PAR6 and aPKC, recruiting aPKC to cell-cell contacts and developing the apical domain. This complex also links GTP-bound Rho small GTPases to aPKC proteins. Pard3 also regulates the Hippo signaling pathway, which controls cell proliferation and tissue development, by affecting the activity of proteins like LATS1 and TAZ.
Pard3’s Role in Health and Illness
Proper Pard3 functioning is important for healthy tissue development and maintenance. When Pard3 malfunctions, it can have consequences for overall health due to its role in cell polarity and organizing cellular processes. Disruption in cell polarity, often linked to Pard3 malfunction, is a hallmark of certain diseases.
Pard3 is significantly connected to cancer. Disrupted Pard3 function can contribute to uncontrolled cell growth and tumor formation. In some cancers, like squamous lung cancer, PARD3 gene inactivation leads to errors in cell orientation and contact, promoting tumor development. Restoring Pard3 levels in these cells has been shown to reduce the risk of metastasis.
Pard3’s role in cancer is complex; it can act as both a tumor suppressor and, in some contexts, a tumor promoter, depending on the cancer type and physiological conditions. Loss of Pard3 has been linked to increased proliferation and metastasis in various tumor cells, including breast, thyroid, and lung adenocarcinoma. Pard3 dysfunction has also been associated with neurological disorders, including neural tube defects (congenital malformations of the central nervous system). Variants of Pard3 have also been associated with neurodevelopmental disorders, indicating its involvement in normal brain development and function.