Disease relevance of Amph1

• Dephosphorylation of amphiphysin I requires extracellular Ca2+ and is unaffected by pretreatment of synaptosomes with tetanus toxin [1].
• Improved antifungal activity and reduced toxicity of Amph B solubilized in MM may be due to higher cellular uptake of the drug by fungal cells of infected tissues from MM formulations [2].
• The authors report a 71-year-old woman with amphiphysin-associated paraneoplastic stiff-person syndrome, opsoclonus, and encephalopathy [3].

Psychiatry related information on Amph1

• After in vivo electroconvulsive shock (ECS) in the rat cerebellum, we found an electrophoretic mobility retardation of Amph2, which suggested an increased degree of phosphorylation above the non-stimulated level [4].
• The synaptic protein synaptosomal-associated protein-25 (SNAP25) is decreased whereas amphiphysin is phosphorylated after sleep deprivation [5].

High impact information on Amph1

• Synaptojanin is the only other major brain protein besides dynamin that binds the SH3 domain of amphiphysin, a presynaptic protein with a putative function in endocytosis [6].
• Phosphorylation was proposed to regulate the assembly of an endocytic protein complex with amphiphysin or endophilin [7].
• Pseudophosphorylation of Ser-774 or Ser-778 inhibited syndapin binding without affecting amphiphysin recruitment [7].
• Capacitance measurements of membrane retrieval were made in terminals in which peptides and protein domains were introduced to disrupt known interactions of clathrin, the AP2 adaptor complex, and amphiphysin [8].
• A major physiological binding partner for dynamin I and synaptojanin in the nervous system is amphiphysin I, an SH3 domain-containing protein also concentrated in nerve terminals [9].

Biological context of Amph1

• Like Amph1, a role in endocytosis at the nerve terminal is supported by the rapid dephosphorylation of Amph2 on depolarization [10].
• However, when Mnbk/Dyrk1A phosphorylation was allowed to proceed more extensively, the phosphorylation enhanced rather than reduced the binding of dynamin 1 to amphiphysin 1 [11].
• We hypothesize that the parallel Ca2+-dependent calcineurin-dependent dephosphorylation of amphiphysin I and of its two major binding proteins is part of a process that primes the nerve terminal for endocytosis in response to a burst of exocytosis [1].
• Accumulations of amphiphysin and synaptojanin immunoreactivities at the crush site were detected as short as 1 h after the lesion, indicating that a pool of these two partially cytosolic proteins moves along the axon by fast axoplasmic transport [12].
• Expression of a mutant amphiphysin harboring two amino acid substitutions in the SH3 domain, and therefore unable to bind proline-containing motifs, induces an accumulation of large intracellular aggregates including amphiphysin, clathrin, AP-2, and other endocytic proteins, as well as a concomitant block of transferrin endocytosis [13].

Anatomical context of Amph1

• COS cells transfected with either Amph1 or Amph2 show greatly reduced transferrin uptake, but coexpression of the two proteins rescues this defect, supporting a role for the heterodimer in clathrin-mediated endocytosis [10].
• Amphiphysin (Amph) is a src homology 3 domain-containing protein that has been implicated in synaptic vesicle endocytosis as a result of its interaction with dynamin [10].
• Expression of the endocytic proteins dynamin and amphiphysin in rat gastric enterochromaffin-like cells [14].
• Our findings suggest a conserved role of the amphiphysin protein family in the dynamics of the cortical cell cytoskeleton and provide new evidence for a close functional link between amphiphysin I and dynamin I [15].
• Amphiphysin I antisense oligonucleotides inhibit neurite outgrowth in cultured hippocampal neurons [15].

Associations of Amph1 with chemical compounds

• Dephosphorylation of amphiphysin I, like dephosphorylation of dynamin I and synaptojanin I, is inhibited by cyclosporin A and FK-506 (0.5 microM), two drugs that specifically block the Ca2+/calmodulin-dependent phosphatase 2B calcineurin, but not by okadaic acid (1 microM), which blocks protein phosphatases 1 and 2B [1].
• Synaptojanin is a nerve-terminal enriched inositol 5-phosphatase thought to function in synaptic vesicle endocytosis, in part through interactions with the Src homology 3 domain of amphiphysin [16].
• In adult testes reversibly damaged by ethane dimethane sulphonate administration, expression of amphiphysin I did not change following the damage, whereas the protein was transiently converted into its phosphorylated form [17].
• The MM formulations of Amph B were prepared using sodium deoxycholate (NDC)/sodium taurocholate (NTC)/sodium cholate (NC), and HSPC [2].
• The purpose of the study was to develop a stable, controlled release Amphotericin B (Amph B) lyophilized mixed micelle (MM) formulation using hydrogenated soya phosphatidylcholine (HSPC) and bile salts in monomeric form and evaluate it for therapeutic performance and side effects [2].

Regulatory relationships of Amph1

• Amphiphysin-dependent clathrin-coat recruitment is enhanced by the interaction of amphiphysin with dynamin [13].

Other interactions of Amph1

• Amphiphysin-1 and -2 were also detected in enterochromaffin-like cells by immunohistochemistry in the same locations as dynamin-1 and -2 [14].
• Upon Mnbk/Dyrk1A phosphorylation, the interaction of dynamin 1 with the Src homology 3 domain of amphiphysin 1 was reduced [11].
• An essential mediator of calcium's effect is calcineurin, the activation of which leads to dephosphorylation of at least four proteins implicated in endocytosis-dynamin, amphiphysin 1, amphiphysin 2 and synaptojanin [18].
• By contrast, recruitment of GFP chimeras of clathrin, epsin, and amphiphysin was not observed [19].
• Amphiphysin 1 is a brain-specific protein enriched at the synapse and a major binding partner of several components of the clathrin-mediated endocytic machinery (Proc Natl Acad Sci USA 93 (1996) 331) [13].

Analytical, diagnostic and therapeutic context of Amph1

• The presence of amphiphysin-1 and -2 RNAs was revealed by RT-PCR and a new splice variant of amphiphysin-2 was detected [14].
• By immunoprecipitation and double-immunolabelling, amphiphysin Ir was shown to be associated not only with amphiphysin II, but also with dynamin, clathrin and alpha-adaptin that are involved in synaptic vesicle recycling [20].
• Cellular distribution of Amph was visualized with confocal immunofluorescence microscopy performed using the labeled-mAbs [21].
• Western blot analysis revealed that amphiphysin I levels steadily increased with neuronal differentiation, whereas in antisense-treated cultures amphiphysin I levels were reduced to approximately 10% of control levels at 48 hr [15].

References