Table 1.

Sorting mechanisms for constitutive and regulated apical protein delivery

Apical protein Sorting signal Presumed sorting mechanism MT motor References
Constitutive apical transport
   Influenza HA TM domain Lipid-raft-association; raft clustering by MAL1, MAL2 and FAPP2 KIFC3 (Rodriguez-Boulan and Pendergast, 1980; Lin et al., 1998; Puertollano et al., 1999; Scheiffele, 1997)
   GPI-anchored proteins (e.g. decay-accelerating F factor, folate receptor, GFP-GPI, 5′-nucleotidase, CEA) GPI Lipid-raft association and oligomerization; raft clustering by MAL1, MAL2, FAPP2 and galectin-4 ? (Lisanti et al., 1989a; Brown et al., 1989; Brown and Rose, 1992; de Marco et al., 2006; Delacour et al., 2005; Hannan et al., 1993; Paladino et al., 2008; Paladino et al., 2004; Puertollano et al., 1999; Vieira et al., 2005)
   p75 neurotrophin receptor O-glycosylated stalk Clustering by galectin-3; raft-independent KIF5B (Yeaman et al., 1997; Delacour et al., 2007; Jaulin et al., 2007)
   Lactase-phlorizin hydrolase O-glycans Clustering by galectin-3; raft-independent ? (Delacour et al., 2006)
   Sucrase-isomaltase TM domain Raft association ? (Jacob et al., 2000)
   Endolyn N-glycans Raft-independent ? (Potter et al., 2004)
   Rhodopsin Cytoplasmic domain Dynein light chain; raft-independent Dynein (Chuang and Sung, 1998; Tai et al., 1999)
   pIgR Apical and basolateral signals Raft-independent; MAL2 ? (Luton et al., 2009)
   Syntaxins 1,2,3 FMDE in cytoplasmic domain ? ? (Sharma et al., 2006)
   Megalin NPXY-like motifs Clathrin adaptors? ? (Marzolo et al., 2003; Takeda et al., 2003)
   Prominins 1,2 TM domain? Lubrol-insoluble rafts? ? (Corbeil et al., 2001; Florek et al., 2007)
   Soluble proteins (e.g. growth hormone, erythropoietin, hepatitis virus antigen) N-glycans, protein motifs Receptors? ? (Marzolo, 1997; Potter et al., 2006; Rodriguez-Boulan and Gonzalez, 1999; Scheiffele et al., 1995)
   Na+-K+ ATPase, CD147, MCT1, CAR, apical proteins in renal PCT Recessive apical signals Absence of basolateral adaptors ? (Gundersen et al., 1991; Deora et al., 2005; Diaz et al., 2009) (Ryan Schreiner and E.R.-B., unpublished data)
Regulated apical transport
   Vacuolar H+ ATPase ? ? Regulated by metabolic pH, basal-membrane contacts and hensin ? (Brown et al., 2009; Schwartz and Al-Awqati, 2005)
   Gastric H+ ATPase TM domain ? Regulated by gastric content and histamine ? (Muth and Caplan, 2003)
   CFTR, Na-Pi cotransporter, GAT3 PDZ-binding motif PDZ-domain-containing proteins ? (Muth and Caplan, 2003)
   Aquaporin 2 ? ? Regulated by ADH ? (Brown et al., 2009)
   Na, PiIIa ? ? Regulated by PTH ? (Muth and Caplan, 2003)
   Epithelial Na+ channel ? ? Regulated by aldosterone, vasopressin (Muth and Caplan, 2003)
   ATP transporters (BSEP, MDR1, MDR3, ABCG5/8) TM domain? Lubrol-insoluble rafts; regulated by various mechanisms ? (Hoekstra et al., 2004; Slimane et al., 2003; Wakabayashi et al., 2006)
   ATP7B (Menkes) copper transporter ? ? Regulated by copper levels ? (Kim et al., 2008)
  • ADH, antidiuretic hormone; CAR, coxsackie-adenovirus receptor; CEA, carcinoembryonic antigen; CFTR, cystic fibrosis transmembrane conductance regulator; FAPP, phosphatidylinositol 4-phosphate adaptor protein; GAT, γ-aminobutyric acid transporter; GFP, green fluorescent protein; GPI, glycosylphosphatidylinositol; HA, hemagglutinin; MAL, myelin and lymphocyte protein; MCT, monocarboxylate transporter; PCT, proximal convoluted tubule; PDZ domain, postsynaptic density protein-95/discs large/zonula occludens domain; pIgR, polymeric immunoglobulin receptor; PTH, parathyroid hormone