Ca2+/H+ exchange by acidic organelles regulates cell migration in vivo

Increasing evidence implicates Ca(2+)in the control of cell migration. However, the underlying mechanisms are incompletely understood. Acidic Ca(2+)stores are fast emerging as signaling centers. But how Ca(2+)is taken up by these organelles in metazoans and the physiological relevance for migration is unclear. Here, we identify a vertebrate Ca(2+)/H(+)exchanger (CAX) as part of a widespread family of homologues in animals. CAX is expressed in neural crest cells and required for their migration in vivo. It localizes to acidic organelles, tempers evoked Ca(2+)signals, and regulates cell-matrix adhesion during migration. Our data provide new molecular insight into how Ca(2+)is handled by acidic organelles and link this to migration, thereby underscoring the role of noncanonical Ca(2+)stores in the control of Ca(2+)-dependent function

The LysE Superfamily of Transport Proteins Involved in Cell Physiology and Pathogenesis

The LysE superfamily consists of transmembrane transport proteins that catalyze export of amino acids, lipids and heavy metal ions. Statistical means were used to show that it includes newly identified families including transporters specific for (1) tellurium, (2) iron/lead, (3) manganese, (4) calcium, (5) nickel/cobalt, (6) amino acids, and (7) peptidoglycolipids as well as (8) one family of transmembrane electron carriers. Internal repeats and conserved motifs were identified, and multiple alignments, phylogenetic trees and average hydropathy, amphipathicity and similarity plots provided evidence that all members of the superfamily derived from a single common 3-TMS precursor peptide via intragenic duplication. Their common origin implies that they share common structural, mechanistic and functional attributes. The transporters of this superfamily play important roles in ionic homeostasis, cell envelope assembly, and protection from excessive cytoplasmic heavy metal/metabolite concentrations. They thus influence the physiology and pathogenesis of numerous microbes, being potential targets of drug action