title: MAL2 selectively regulates polymeric IgA receptor delivery from the Golgi to the plasma membrane in WIF-B cells.
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.
authors.affiliation: Department of Biology, The Catholic University of America, Washington, DC 20064, USA.
authors.forename: Julie G
authors.initials: JG
authors.lastname: In
authors.forename: Pamela L
authors.initials: PL
authors.lastname: Tuma
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011961:Receptors, Fc / Q000235:genetics / Q000378:metabolism*; D019056:Receptors, Polymeric Immunoglobulin / Q000235:genetics / Q000378:metabolism*
chemical_list: C045281:IgA receptor; C569026:MAL protein, human; C569028:Mal protein, rat; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D020033:Protein Isoforms; D011510:Proteolipids; D011961:Receptors, Fc; D019056:Receptors, Polymeric Immunoglobulin; D018819:Dipeptidyl Peptidase 4
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