Macropinocytosis is increasingly recognized for its versatile adaptations and functions as a highly conserved, ubiquitous pathway for the bulk uptake of fluid, particulate cargo, and membranes. Innate immune cells and transformed cancer cells share the capacity for both constitutive and induced macropinocytosis, which is used for immune surveillance, ingestion of pathogens, immune response shaping, and enhancement of scavenging for nutrients as fuel for cell survival and proliferation. Immunology and cancer biology are leading a resurgence of interest in defining the molecular and physiological regulation of macropinocytosis, partly in pursuit of ways to control macropinocytic uptake in disease settings. New approaches, including high-resolution live imaging, screening of cell surface molecular inventories, biophysics, and exploration of cell microenvironments, have converged to provide new insights into macropinosome induction, formation, and maturation. Recent studies reveal mechanisms for fluid control in and by macrophage macropinosomes that impinge on membrane trafficking and cell migration. EGFR, PTEN, V-ATPase, syndecan 1, and galectin-3 have roles variably in the metabolic regulation of Ras or PI3K signaling for Rac1-mediated macropinocytosis in cancer. These molecular pathways and mechanisms contribute to the impressive adaptability of macropinocytosis in many cells and tissues and in disease.

The developing cochlea of mammals contains a large group of columnar-shaped cells, which together form a structure known as Kölliker\'s organ. Prior to the onset of hearing, these inner supporting cells periodically release adenosine 5\'-triphosphate (ATP), which activates purinergic receptors in surrounding supporting cells, inner hair cells and the dendrites of primary auditory neurons. Recent studies indicate that purinergic signaling between inner supporting cells and inner hair cells initiates bursts of action potentials in auditory nerve fibers before the onset of hearing. ATP also induces prominent effects in inner supporting cells, including an increase in membrane conductance, a rise in intracellular Ca(2+), and dramatic changes in cell shape, although the importance of ATP signaling in non-sensory cells of the developing cochlea remains unknown. Here, we review current knowledge pertaining to purinergic signaling in supporting cells of Kölliker\'s organ and focus on the mechanisms by which ATP induces changes in their morphology. We show that these changes in cell shape are preceded by increases in cytoplasmic Ca(2+), and provide new evidence indicating that elevation of intracellular Ca(2+) and IP(3) are sufficient to initiate shape changes. In addition, we discuss the possibility that these ATP-mediated morphological changes reflect crenation following the activation of Ca(2+)-activated Cl(-) channels, and speculate about the possible functions of these changes in cell morphology for maturation of the cochlea.