Plxnc1Edit
PLXNC1, or Plexin-C1, is a human gene encoding a receptor in the plexin family that participates in semaphorin signaling. Plexin-C1 is a transmembrane protein that contributes to guidance cues governing cell movement and axon pathfinding during development, while also playing roles in immune cell behavior and, in some cancer contexts, in tumor cell migration and invasion. The plexin-semaphorin signaling axis is conserved across vertebrates and helps organize tissue architecture by directing cytoskeletal dynamics through small GTPases. The gene is expressed in a variety of tissues, including neural tissue, certain immune cell populations, and vascular beds, which underlines its multifunctional contributions to physiology.
Biology and function
Molecular structure
Plexin-C1 is a member of the plexin receptor family, with an extracellular sema domain responsible for ligand recognition, followed by adjacent domains and a single-pass transmembrane segment. Its cytoplasmic region contains a Ras GAP–like domain that interfaces with small guanine nucleotide–binding proteins of the Rho family, translating extracellular semaphorin cues into intracellular cytoskeletal rearrangements. The architecture of Plexin-C1 mirrors the general design of plexins, distinguishing it from other receptor families that couple to Guidance signaling in different ways. See also Plexin for broader context on this receptor family.
Ligands and signaling
The primary ligands for Plexin-C1 are members of the semaphorin family, most notably Semaphorin-7A. Binding of semaphorins to Plexin-C1 initiates intracellular signaling cascades that regulate actin dynamics, cell adhesion, and motility. This signaling can influence processes from axon guidance in development to immune cell behavior in adult tissues, and it intersects with multiple signaling pathways involving Rho family GTPases such as Rho GTPases and their regulators. For broader background on the signaling system, see Semaphorin.
Expression and tissue distribution
Expression data indicate that PLXNC1 is found in diverse tissues, including parts of the nervous system, subsets of immune cells, and endothelial or epithelial compartments in various organs. This distribution supports a role for Plexin-C1 in coordinating cellular movement and tissue organization across multiple physiological contexts. Readers may consult general resources on gene expression for further detail, such as Gene expression and tissue-specific expression databases linked from Human biology.
Clinical significance
Neurodevelopment and immune function
Given its role in guiding cellular movement and cytoskeletal changes, PLXNC1 participates in neurodevelopmental processes that shape neural connectivity. In the immune system, semaphorin-plexin signaling can modulate cell migration and activation states of certain leukocyte populations, aligning immune responses with tissue needs and developmental cues. See also Neurodevelopment and Immune system for related topics.
Cancer and metastasis
Plexin-C1 has attracted attention for potential involvement in cancer biology. Across cancer types, the role of PLXNC1 appears to be context-dependent and sometimes paradoxical. In some settings, Plexin-C1 signaling may act to restrain tumor cell movement and invasion, consistent with a tumor-suppressive function under particular ligand environments and tissue contexts. In other situations, Plexin-C1–semaphorin signaling can promote migratory and invasive behaviors, contributing to metastatic potential. These contrasting observations reflect the complexity of semaphorin-plexin signaling, including how ligand availability, receptor expression levels, and interactions with other receptors shape outcomes. For readers exploring cancer biology, see Cancer and Metastasis; you may also encounter specific discussions about Colorectal cancer where plexin-semaphorin axis has been studied. The evolving literature emphasizes that therapeutic strategies targeting this axis must consider tissue type, stage, and microenvironment.
Therapeutic implications and debates
As researchers map the pleiotropic effects of semaphorin-plexin signaling, there is ongoing debate about how best to harness this axis for therapy. Potential approaches include modulating Plexin-C1 activity to influence tumor cell motility or to adjust immune cell behavior within the tumor microenvironment. The complexity of context-dependent effects means that blanket activation or inhibition of Plexin-C1 is unlikely to be universally beneficial. See also Therapeutic discussions in cancer research for related considerations.
Evolution and comparative biology
Plexin receptors, including Plexin-C1, are part of a conserved signaling system present across vertebrates, with variations in ligand repertoires and tissue-specific roles. Comparative studies help illuminate how semaphorin-plexin signaling coordinates development and tissue organization across species. See Evolution and Comparative genomics for broader context.