MAL2 selectively regulates polymeric IgA receptor delivery from the Golgi to the plasma membrane in WIF-B cells.

Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
Traffic (Impact Factor: 4.71). 04/2010; 11(8):1056-66. DOI: 10.1111/j.1600-0854.2010.01074.x
Source: PubMed

ABSTRACT Myelin and lymphocyte protein 2 (MAL2) has been identified as a hepatic transcytotic regulator that mediates delivery from basolateral endosomes to the subapical compartment (SAC). However, overexpression of polymeric immunoglobulin A-receptor (pIgA-R) in polarized, hepatic WIF-B cells led to the dramatic redistribution of MAL2 into the Golgi and all the transcytotic intermediates occupied by the receptor. Although overexpressed hemagglutinin and dipeptidylpeptidase IV (DPPIV) distributed to the same compartments, MAL2 distributions did not change indicating the effect is selective. Cycloheximide treatment led to decreased pIgA-R and MAL2 intracellular staining, first in the Golgi then the SAC, suggesting they were apically delivered and that MAL2 was mediating the process. This was tested in Clone 9 cells (that lack endogenous MAL2). When expressed alone, pIgA-R was restricted to the Golgi whereas when coexpressed with MAL2, it distributed to the surface, was internalized and delivered to MAL2-positive puncta. In contrast, DPPIV distributions were independent of MAL2. Surface delivery of newly synthesized pIgA-R, but not DPPIV, was enhanced greater than ninefold by MAL2 coexpression. In WIF-B cells where MAL2 expression was knocked down, pIgA-R, but not DPPIV, was retained in the Golgi and its basolateral delivery was impaired. Thus, in addition to its role in transcytosis, MAL2 also regulates pIgA-R delivery from the Golgi to the plasma membrane.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocytes, the main epithelial cell type of the liver, function like all epithelial cells to mediate the vectorial flow of macromolecules into and out of the organ they encompass. They do so by establishing polarized surface domains and by restricting paracellular flow via their tight junctions and cell-cell adhesion. Yet, the cell and tissue organization of hepatocytes differs profoundly from that of most other epithelia, including those of the digestive and urinary tracts, the lung or the breast. The latter form monolayered tissues in which the apical domains of individual cells align around a central continuous luminal cavity that constitutes the tubules and acini characteristic of these organs. Hepatocytes, by contrast, form capillary-sized lumina with multiple neighbors resulting in a branched, tree-like bile canaliculi network that spreads across the liver parenchyme. I will discuss some of the key molecular features that distinguish the hepatocyte polarity phenotype from that of monopolar, columnar epithelia.
    Experimental Cell Research 11/2014; · 3.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocytes, like other epithelia, are situated at the interface between the organism's exterior and the underlying internal milieu and organize the vectorial exchange of macromolecules between these two spaces. To mediate this function, epithelial cells, including hepatocytes, are polarized with distinct luminal domains that are separated by tight junctions from lateral domains engaged in cell-cell adhesion and from basal domains that interact with the underlying extracellular matrix. Despite these universal principles, hepatocytes distinguish themselves from other nonstriated epithelia by their multipolar organization. Each hepatocyte participates in multiple, narrow lumina, the bile canaliculi, and has multiple basal surfaces that face the endothelial lining. Hepatocytes also differ in the mechanism of luminal protein trafficking from other epithelia studied. They lack polarized protein secretion to the luminal domain and target single-spanning and glycosylphosphatidylinositol-anchored bile canalicular membrane proteins via transcytosis from the basolateral domain. We compare this unique hepatic polarity phenotype with that of the more common columnar epithelial organization and review our current knowledge of the signaling mechanisms and the organization of polarized protein trafficking that govern the establishment and maintenance of hepatic polarity. The serine/threonine kinase LKB1, which is activated by the bile acid taurocholate and, in turn, activates adenosine monophosphate kinase-related kinases including AMPK1/2 and Par1 paralogues has emerged as a key determinant of hepatic polarity. We propose that the absence of a hepatocyte basal lamina and differences in cell-cell adhesion signaling that determine the positioning of tight junctions are two crucial determinants for the distinct hepatic and columnar polarity phenotypes. © 2013 American Physiological Society. Compr Physiol 3:243-287, 2013.
    Comprehensive Physiology. 01/2013; 3(1):243-287.
  • [Show abstract] [Hide abstract]
    ABSTRACT: One puzzle in international finance is the finding that the forward foreign exchange rate is a poor predictor of the future spot foreign exchange rate. It has been postulated that this finding could be explained by the presence of unobservable risk premiums. Theory, however, is silent as to the factors that proxy for these risk premiums. Thus, we examine spot and forward bid-ask spreads and deviations from relative PPP as potential proxies. We find statistically significant evidence that deviations from relative PPP are related to the forward prediction error for the British pound and the euro. Furthermore, when examining the British pound exchange rates with the currencies of developed countries, we find that the coefficients on the bid-ask spreads are significant for the entire period. The coefficients on the bid-ask spreads of euro exchange rates with the currencies of developed countries are significant during the period 1999 to 2007. The findings are robust with respect to several different terms of forward rates, the consideration of transactions costs by using bid and spot rates instead of midpoint rates, and controlling for possible asymmetry and non-linearity.
    The Quarterly Review of Economics and Finance 07/2014; 55.

Full-text (2 Sources)

Available from
Oct 14, 2014