Disease relevance of Ap2m1

• Enzyme-linked immunosorbent binding assays showed that these phages specifically recognized peptides containing functional leucine- and tyrosine-based sorting signals, suggesting that these regions of the mu1 and mu2 chains interact with both types of sorting signals [1].
• These results suggest that both mu1 and mu2 receptors contribute to opioid-induced respiratory depression during neonatal and adult life [2].

Psychiatry related information on Ap2m1

• The data suggest that mu1-opioid receptors are responsible for the low dose stimulant effects of dermorphin on locomotor activity and respiration whereas mu2 receptors mediate the respiratory depressant effect of dermorphin [3].

High impact information on Ap2m1

• Two potential polyphosphatidylinositide binding sites are observed, one on alpha and one on mu2 [4].
• Many cell surface proteins are marked for endocytosis by a cytoplasmic sequence motif, tyrosine-X-X-(hydrophobic residue), that is recognized by the mu2 subunit of AP2 adaptors [5].
• Crystal structures of the internalization signal binding domain of mu2 complexed with the internalization signal peptides of epidermal growth factor receptor and the trans-Golgi network protein TGN38 have been determined at 2.7 angstrom resolution [5].
• In stimulated frog mucosa the corresponding values were 3 X 10(8) molecules of HCl per cell per sec 2 X 10(5) molecules per sec per mu2 or secretory surface [6].
• The best understood of these interactions occurs between the tyrosine-based motif, YXXPhi, and the mu2 subunit of AP-2 [7].

Biological context of Ap2m1

• We have tested whether this phosphorylation has any effect on the interaction of mu2 with the tyrosine based motif containing protein, TGN38, that has previously been shown to interact with mu2 [8].
• Previous studies using selective subtype antagonists indicated that opioid effects upon deprivation-induced water intake occurred through the mu2 receptor and that opioid effects upon sucrose intake occurred through kappa and mu2 receptors [9].
• Since the presence of 100 mM NaCl during the competitive binding decreased the K(i), to varying degrees, of all five opioids at the mu1 and delta receptors and of some of the opioids at the mu2 and kappa1 receptors, the five compounds studied appear to differ in efficacy at the five receptor sites [10].

Anatomical context of Ap2m1

• We have used a combination of surface plasmon resonance and crosslinking with a photoactivated peptide probe to demonstrate the interaction between FDNPVY-containing peptides and the mu2 chain of purified AP-2 clathrin adaptors (the complexes responsible for plasma membrane sorting) [11].
• Yeast two-hybrid analyses revealed that the N-terminal phenylalanine-based targeting signal in GLUT4 constitutes a binding site for medium chain adaptins mu1, mu2, and mu3A, implicating a role of this motif in the targeting of GLUT4 to clathrin-coated vesicles [12].
• Gender differences were not observed for mu1, mu2, or delta binding in hypothalamus or cortex [13].
• Autoradiographic distribution of mu1 and mu2 opioid binding in the mouse central nervous system [14].
• High ratios of mu1 to mu2 binding were noted in frontal cortex, nucleus accumbens, rostral striatum, ventral pallidum, ventral periaqueductal gray matter, and laminae I and II of the spinal cord [14].

Associations of Ap2m1 with chemical compounds

• We show that recognition of the FDNPVY signal is mediated by a binding site in the mu2-subunit that is distinct from the site for the more general YppØ sorting signal, another tyrosine-based sequence also recognized by mu2-adaptin [11].
• In addition, the P-selectin peptide binds to a third hydrophobic pocket in mu 2 adaptin through a leucine at position Y-3 in the peptide [15].
• These observations reveal a functional similarity between the tryptophan-based endocytosis signal and the YXXPhi motif, and an unexpected versatility of mu2 function [7].
• These data implicate mu2, kappa and delta1 sites in the opioid modulation of isoproterenol drinking [16].
• Despite its significant effects relative to naloxonazine, B-FNA had significantly higher ID40 values for saccharin (800 nmol), MD (763 nmol) and sucrose (508 nmol) relative to deprivation (99 nmol) intake, suggesting that mu2 receptors may be mediating maintenance of intake rather than taste effects [9].

Other interactions of Ap2m1

• To address this apparent discrepancy, we employed siRNA to suppress expression of components of the clathrin-mediated internalization machinery, namely, clathrin heavy chain, and the AP-2 (alpha-adaptin or mu2-subunit) [17].

Analytical, diagnostic and therapeutic context of Ap2m1

• We have used quantitative in vitro autoradiography to compare the levels of mu1 and mu2 opioid binding in the mouse central nervous system [14].
• Monoclonal DNP-specific IgG (lambda 2 epsilon 2), IgM (kappa 2 mu2) and IgG [kappa 2 (gamma 1)2] were isolated fom the culture supernatant of hybridomas by affinity chromatography with 2,4-dinitrophenol bovine serum albumin (DNP-BSA) sepharose and characterized by biochemical and biological methods [18].
• In contrast two mu2 actions, respiratory depression measured with arterial blood gas, determinations and gastrointestinal transit, showed no significant tolerance over a similar 8 hr infusion [19].

References