GO:0015847 putrescine transport: Genes and Methods

GO:0015847 putrescine transport is the biological process defined as the directed movement of putrescine into, out of, or within a cell, or between cells, by means of some agent such as a transporter or pore [2, 3]. Putrescine is 1,4-diaminobutane, the polyamine formed by decarboxylation of ornithine and the metabolic precursor of spermidine and spermine [2, 7]. Because polyamines are charged at physiological pH and cannot freely diffuse across lipid bilayers, dedicated transport systems are required to move putrescine between compartments and across membranes [2, 3]. This makes putrescine transport a central node in polyamine biology rather than a passive housekeeping step. Researchers study GO:0015847 because putrescine availability influences proliferation, stress signaling, and epithelial barrier physiology [5, 6, 7]. In human platelets, putrescine transport has been characterized as a saturable carrier-mediated process, establishing that specific transport machinery exists in blood cells. In differentiated Caco-2 intestinal epithelial cells, putrescine transport has been measured across cell monolayers, providing a model for how dietary and microbial polyamines reach the circulation [4, 6]. In chicks, putrescine transport has been mapped across duodenal, jejunal, and ileal brush-border membranes, showing regional specialization of intestinal polyamine uptake. At the subcellular level, ATP13A2 deficiency disrupts lysosomal polyamine export, demonstrating that putrescine and related polyamines must be moved out of lysosomes by dedicated machinery. In hypoxic rat main pulmonary arterial smooth muscle cells, putrescine transport is required for p38 MAP kinase activation, linking uptake to a defined signaling output. In proliferating human fibroblasts, putrescine transport is greatly increased upon initiation of proliferation, tying transport capacity to growth state. Together, these studies define GO:0015847 as a measurable, regulated, and disease-relevant transport process.

In plain terms, GO:0015847 putrescine transport is the process by which a cell moves putrescine from one side of a membrane to the other, or between cellular compartments, using a transporter or pore [2, 3]. The QuickGO definition specifies that the movement is directed and can occur into, out of, or within a cell, or between cells [2, 3]. Putrescine itself is 1,4-diaminobutane, produced by decarboxylation of ornithine and used as the precursor for spermidine and spermine [2, 7]. The term therefore covers plasma-membrane uptake and efflux as well as intracellular translocation such as lysosomal export. It does not describe putrescine biosynthesis or the downstream conversion of putrescine into spermidine and spermine; those are separate metabolic processes [2, 7].

GO:0015847 putrescine transport matters because putrescine is both a metabolic precursor of spermidine and spermine and a signaling-relevant polyamine, so its distribution across membranes determines whether cells can grow, respond to stress, and maintain epithelial and lysosomal function [2, 5, 7]. Transport is not a passive consequence of synthesis: in human fibroblasts, putrescine transport increases greatly when cells are initiated to proliferate, and in hypoxic pulmonary arterial smooth muscle cells it is required for p38 MAP kinase activation [5, 7]. In epithelia, transepithelial putrescine movement across Caco-2 monolayers and regional transport across chick intestinal brush-border membranes show that uptake is organized and site-specific [6, 8]. In lysosomes, ATP13A2-dependent polyamine export demonstrates that intracellular putrescine movement is genetically encoded and can be disrupted in disease.

The following genes and proteins have been experimentally implicated in putrescine transport or in the transport of closely related polyamines in the cited systems.

Putrescine transport is regulated by growth state and by oxygen availability. In human fibroblasts initiated to proliferate, putrescine transport is greatly increased, indicating that transport capacity is coupled to the quiescence-to-proliferation transition. In hypoxic rat main pulmonary arterial smooth muscle cells, putrescine transport is required for p38 MAP kinase activation, placing transport upstream of a stress-activated kinase module. At the organelle level, ATP13A2-dependent lysosomal polyamine export shows that intracellular putrescine movement is genetically regulated and can be disrupted by loss of a single transporter. In epithelial models, transepithelial putrescine transport across Caco-2 monolayers and regional transport across chick intestinal brush-border membranes indicate that regulation also differs by tissue segment [6, 8]. Metabolic modeling of single Th17 cells has revealed regulators of autoimmunity, providing a framework for studying how metabolic and transport states are controlled in immune cells.

ATP13A2 deficiency disrupts lysosomal polyamine export, directly linking a defect in intracellular putrescine and polyamine movement to lysosomal dysfunction. Because GO:0015847 includes movement within a cell, this finding places putrescine transport within the mechanistic space of lysosomal storage and neurodegeneration-related biology. The observation that loss of ATP13A2 traps polyamines in lysosomes provides a clear genotype-to-cell-biology link for experimental modeling.

In hypoxic rat main pulmonary arterial smooth muscle cells, putrescine transport is required for p38 MAP kinase activation. This connects GO:0015847 to stress signaling in the pulmonary vasculature and suggests that transport inhibitors or transporter knockouts could be used to test whether p38-dependent responses require putrescine uptake. The finding also implies that hypoxic conditions change the requirement for putrescine transport rather than merely changing putrescine levels.

Transepithelial transport of putrescine across Caco-2 monolayers and regional putrescine transport across chick duodenal, jejunal, and ileal brush-border membranes show that the intestine is a major site of putrescine handling [6, 8]. Differentiated Caco-2 cells transport putrescine, making them a standard model for epithelial polyamine flux. These systems are relevant to understanding how dietary and microbial polyamines are absorbed and how epithelial transport capacity varies along the gut [4, 6, 8].

Putrescine transport is greatly increased in human fibroblasts initiated to proliferate, linking GO:0015847 to growth control. Metabolic modeling of single Th17 cells has revealed regulators of autoimmunity, showing that polyamine-related metabolic states can be resolved in immune cells. Together these findings support the idea that putrescine transport contributes to proliferative and immune-metabolic programs, although the precise transporter genes in those settings require further experimental definition [1, 7].

Direct measurement of putrescine transport has been performed in human platelets, differentiated Caco-2 cells, rat pulmonary arterial smooth muscle cells, human fibroblasts, and chick intestinal brush-border membranes [3, 4, 5, 6, 7, 8]. These assays quantify uptake or transepithelial flux and can distinguish carrier-mediated from passive movement [3, 6]. They are the primary functional readout for GO:0015847 [3, 4, 5, 6, 7, 8].

Caco-2 monolayers allow directional transepithelial putrescine transport to be measured across a polarized epithelium. Brush-border membrane vesicles from chick duodenum, jejunum, and ileum allow regional transport capacity to be compared directly. Differentiated Caco-2 cells provide a human cell model for epithelial putrescine transport. These systems are well suited to testing whether a candidate gene changes transport direction or capacity [4, 6, 8].

In hypoxic rat main pulmonary arterial smooth muscle cells, putrescine transport is required for p38 MAP kinase activation, so phospho-p38 measurement can be used as a downstream readout of transport function. In proliferation models, transport increases can be correlated with growth-state markers in human fibroblasts. Combining transport assays with signaling readouts helps establish causality rather than correlation [5, 7].

Metabolic modeling of single Th17 cells has revealed regulators of autoimmunity, demonstrating how single-cell metabolic analysis can identify regulatory nodes in polyamine-related biology. Such approaches can be paired with transport assays to connect candidate regulators to putrescine flux. Omics and modeling are therefore complementary to direct transport measurements for GO:0015847 [1, 3].

Researchers studying putrescine transport-related genes often need to determine whether a candidate gene is causally involved in putrescine movement or is merely correlated with it. Because GO:0015847 spans plasma-membrane uptake, transepithelial flux, and intracellular movement such as lysosomal export, the appropriate experimental model depends on the compartment and cell type being studied [2, 4, 6]. EDITGENE provides CRISPR-based cell models and screening services that allow transport hypotheses to be tested directly in relevant cellular backgrounds.

GO:0015847 putrescine transport is a defined biological process covering the directed movement of putrescine across membranes and between cellular compartments [2, 3]. Experimental work in platelets, intestinal epithelial cells, pulmonary arterial smooth muscle cells, fibroblasts, and chick intestinal membranes has established that putrescine transport is carrier-mediated, regionally organized, and regulated by growth and oxygen state [3, 4, 5, 6, 7, 8]. ATP13A2-dependent lysosomal polyamine export shows that intracellular putrescine movement is genetically encoded and can be disrupted in disease. Together, these findings make putrescine transport a tractable and disease-relevant target for CRISPR-based functional studies.