PaxillinEdit

Paxillin is a cytoskeletal adaptor protein that localizes to focal adhesions, the dynamic contact points where cells attach to the extracellular matrix and communicate with their surroundings. Encoded by the PXN gene in humans, paxillin serves as a central coordination hub that links integrin signaling to the actin cytoskeleton and downstream pathways controlling adhesion, migration, and survival. In most cell types, paxillin helps cells sense mechanical cues in their environment and respond by reorganizing their cytoskeleton, which is essential for processes such as development, tissue repair, and immune cell trafficking. Its function as an organizing scaffold at adhesion sites makes paxillin a focal point in both normal physiology and disease-related remodeling of tissues. focal adhesion integrins actin PXN

Paxillin’s role extends beyond simply anchoring cells to the matrix. By assembling signaling complexes at focal adhesions, paxillin coordinates multiple pathways that regulate cell shape, motility, and response to mechanical stress. Because focal adhesions are involved in tissue organization and wound healing, paxillin has been a subject of interest in studies of cancer metastasis and regenerative biology. In addition to its structural role, paxillin participates in signaling networks that influence cell survival and proliferation in response to extracellular cues. signal transduction angiogenesis cancer cell migration

Structure and domains

N-terminal LD motifs

The N-terminus of paxillin contains a series of leucine-rich LD motifs (LD1–LD5) that mediate interactions with a variety of binding partners. These motifs function as recruitment modules for signaling proteins and adaptors, helping assemble complexes at focal adhesions. Through these interactions, paxillin can influence how signals from integrins are transmitted to downstream effectors. LD motifs SH2 domain Crk

C-terminal LIM domains

The C-terminus of paxillin harbors several LIM domains that help target the protein to focal adhesions and stabilize its position within the adhesion complex. The LIM domains contribute to the spatial organization of signaling assemblies and help tether paxillin-associated complexes to the actin-rich cytoskeleton. LIM domains focal adhesion

Phosphorylation and other modifications

Paxillin is subject to post-translational modifications, notably phosphorylation on tyrosine residues such as Tyr31 and Tyr118 in response to signaling activity from upstream kinases like Focal adhesion kinase and Src family kinases. Phosphorylation modulates paxillin’s interactions and the dynamics of adhesion turnover, facilitating coordinated assembly and disassembly of focal adhesions during cell movement. Additional serine/threonine phosphorylation and other modifications further regulate its function in different cellular contexts. phosphorylation FAK Src

Interactions and signaling

Paxillin operates as a scaffolding protein that integrates signals at focal adhesions by binding to a network of kinases, adaptors, and structural proteins. Key interactions include: - FAK and Src kinases, which phosphorylate paxillin and propagate adhesion signaling. - Structural proteins such as talin and vinculin, which link integrins to the actin cytoskeleton and help position paxillin at adhesion sites. - Adaptor proteins like Crk and components of the PI3K pathway, which connect adhesion signaling to cell motility and survival programs. Through these associations, paxillin coordinates the transmission of mechanical and biochemical information from the extracellular environment to the intracellular signaling machinery, influencing actin remodeling, adhesion turnover, and migratory behavior. focal adhesion actin signal transduction

Cellular functions

Adhesion formation and turnover: Paxillin participates in the assembly of focal adhesions at the leading edge of migrating cells and their disassembly at the rear, enabling directed movement. cell migration
Cytoskeletal remodeling: By organizing signaling complexes, paxillin regulates actin dynamics in response to mechanical cues from the extracellular matrix. cytoskeleton
Mechanotransduction: Paxillin helps cells sense stiffness and other physical properties of their surroundings, translating these cues into cellular responses that affect adhesion strength and motility. mechanotransduction
Angiogenesis and tissue remodeling: In endothelial and other cell types, paxillin influences processes that underlie new blood vessel formation and structural adaptation of tissues. angiogenesis
Role in disease contexts: Alterations in paxillin signaling are observed in various diseases, most notably in cancer, where changes in adhesion dynamics can influence metastatic potential, and in wound healing, where efficient adhesion turnover supports tissue repair. cancer wound healing

Regulation and context-dependent roles

Paxillin function is tightly controlled by the balance of kinases and phosphatases at adhesion sites, the mechanical state of the extracellular matrix, and cross-talk with other focal adhesion components. Because focal adhesions integrate biochemical signals with mechanical inputs, paxillin’s activity can have context-dependent outcomes. In some cancer contexts, elevated paxillin signaling correlates with enhanced cell migration and invasion, while in others, the protein may assume a more restrained role depending on the cellular milieu and interacting partners. These nuances reflect the broader complexity of adhesion signaling in tissue homeostasis and disease. cancer cell signaling

Evolution and history

Paxillin is part of a conserved family of focal adhesion adaptor proteins that coordinate cytoskeletal organization and signaling in metazoan cells. Comparative studies across species help illuminate how adhesion complexes adapt to different tissue architectures and mechanical environments. The PXN gene is the human representative encoding the canonical paxillin protein, with homologs in other organisms providing insights into the fundamental architecture of focal adhesions. evolution protein family