Disease relevance of AMPH

• Primary structure of human amphiphysin, the dominant autoantigen of paraneoplastic stiff-man syndrome, and mapping of its gene (AMPH) to chromosome 7p13-p14 [1].
• The comparison of the results obtained by phage display and substitution analysis permitted the identification of proline and arginine at positions 4 and 6 in the PIRPSR and PTIPPR target sequence as the major determinants of the recognition specificity mediated by the SH3 domain of amphiphysin 1 [2].
• The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer [3].
• Autoantibodies against amphiphysin occur in patients afflicted with a rare neurologic autoimmune disease, paraneoplastic Stiff-Man syndrome [1].
• Phosphorylation of amphiphysin I by minibrain kinase/dual-specificity tyrosine phosphorylation-regulated kinase, a kinase implicated in Down syndrome [4].

Psychiatry related information on AMPH

• Periadolescent (PND 33-43) and Adult (PND>60) mice of both sexes were injected with d-amphetamine (AMPH, 0, 2, or 10 mg/kg i.p.) and immediately faced with a mild psychological stress experience, i.e. placement in a novel environment [5].
• AMT may be important in the low dose effects of AMPH such as increased locomotor activity in rodents and stimulant activity in man [6].
• Finally, the possibility that the AMPH cue may generate false positives in screening for drug abuse potential needs to be evaluated [7].
• Both TRH and low amph. increased grooming (perhaps simply by increasing wakefulness), but TRH failed to increase sniffing, a cardinal feature of ampha.-induced excitement [8].

High impact information on AMPH

• BIN1 is structurally related to amphiphysin, a breast cancer-associated autoimmune antigen, and RVS167, a negative regulator of the yeast cell cycle, suggesting roles in malignancy and cell cycle control [9].
• Amphiphysin contains an SH3 domain and is a major dynamin binding partner at the synapse [10].
• The amphiphysin family of proteins and their role in endocytosis at the synapse [11].
• Clathrin-mediated endocytosis at the plasma membrane is a major pathway of synaptic vesicle recycling in neurones, but little is known about the molecular machinery that orchestrates the process.The amphiphysin protein has recently emerged into the limelight since its discovery in 1992 as a synaptic vesicle-associated protein [11].
• GAD and amphiphysin are the only two known targets of CNS autoimmunity with this distribution [3].

Chemical compound and disease context of AMPH

• A randomized, double-blind comparative trial evaluating the safety of liposomal amphotericin B versus amphotericin B lipid complex in the empirical treatment of febrile neutropenia. L Amph/ABLC Collaborative Study Group [12].
• A liposomal preparation of Amph B (LipoAmph B), which is substantially less nephrotoxic, was studied for its ability to enhance platinum-drug toxicity to a human oral squamous cell carcinoma line, HN-5a, and its carboplatin-resistant variant, 5a/carbo-15a, in which cisplatin accumulation was reduced by approximately 40% [13].
• Amphotericin B (Amph B) poorly diffuses from blood into peritoneal fluid, which intraperitoneal administration induces severe abdominal pain [14].

Biological context of AMPH

• Functional partnership between amphiphysin and dynamin in clathrin-mediated endocytosis [15].
• Comparison with chicken amphiphysin defines domains of low and high amino acid sequence conservation [1].
• Here, we report the characterization of a novel amphiphysin isoform (termed amphiphysin II) that was identified through a homology search of the data base of expressed sequence tags [16].
• All the insert sequences were present as unidentified exons in the amphiphysin I gene on human chromosome 7 [17].
• Further analyses showed that during the follicular phase, but not the luteal phase, responses to AMPH were related to levels of estrogen [18].

Anatomical context of AMPH

• Amphiphysin, a protein that is highly concentrated in nerve terminals, has been proposed to function as a linker between the clathrin coat and dynamin in the endocytosis of synaptic vesicles [15].
• In order to elucidate the molecular mechanism underlying the amphiphysin's effect, we measured dynamin GTPase activity in the presence of both amphiphysin 1 and lipid membranes [19].
• Amphiphysin I was also detectable at variable levels in several other human breast cancer tissues and cell lines and at low levels in normal mammary tissue and a variety of other non-neuronal tissues [20].
• Amphiphysin, a neuronal protein first identified in chicken synaptic membranes, is the autoantigen of Stiff-Man Syndrome (SMS) associated with breast cancer [21].
• CONCLUSIONS: The preferential sensitivity of the ventral striatum to the DA releasing effects of AMPH previously demonstrated in experimental animals extends to humans [22].

Associations of AMPH with chemical compounds

• The SH3 domains of endophilin and amphiphysin bind to the proline-rich region of synaptojanin 1 at distinct sites that display an unconventional binding specificity [2].
• We describe here in detail the procedure of the dynamin GTPase assay and the results demonstrating stimulatory effect of amphiphysin on dynamin GTPase activity, which is highly dependent on the liposome size [19].
• Using event-related functional magnetic resonance imaging (fMRI), we conducted a within-subject, double-blind, placebo (PLAC)-controlled study of the effects of oral dextroamphetamine (AMPH, 0.25 mg/kg) treatment on brain activity and affect during incentive processing [23].
• Using positron emission tomography (PET), we correlated the change in endogenous dopamine concentrations following dextroamphetamine (AMPH) administration with the associated hedonic response in human subjects and compared the strength of this correlation across striatal subregions [22].
• Subjects with higher cortisol responses to AMPH also reported more positive subjective drug effects than subjects with lower cortisol responses; no association was observed between cortisol levels and negative drug effects [24].

Physical interactions of AMPH

• Amphiphysin is an SH3 domain-containing neuronal protein that is highly concentrated in nerve terminals where it interacts via its SH3 domain with dynamin I, a GTPase implicated in synaptic vesicle endocytosis [25].
• The extent to which D1 and D2 receptor systems are coupled in AMPH DD assays requires further investigation [7].
• AMAP2 was moreover found to bind to amphiphysin IIm, a component of the endocytic machinery, via its proline-rich domain [26].

Enzymatic interactions of AMPH

• Amphiphysin is phosphorylated by cdk5 in a region including serines 272, 276, and 285 [27].
• These observations are consistent with the hypothesis that, upon activation by nerve growth factor, casein kinase 2 phosphorylates amphiphysin-1 and thereby regulates the endocytosis of clathrin-coated vesicles via the interaction between clathrin and amphiphysin [28].

Regulatory relationships of AMPH

• There was a highly significant (P less than .001; slope = 1.2) linear correlation between the AMT-inhibiting potencies of AMPH analogs and their potencies in stimulating locomotor activity in rodents [6].

Other interactions of AMPH

• We have precisely mapped the target peptides on human synaptojanin that are recognized by the SH3 domains of endophilins and amphiphysin and proven that they are distinct [2].
• The elucidation of clathrin as a splice-specific binding partner for amphiphysin II begins to address the potential functional role(s) for the multiple amphiphysin II splice variants and further supports an important function for clathrin-amphiphysin interactions in protein targeting during endocytosis [29].
• In addition to a single LLDLD-based, type I clathrin-binding sequence, both amphiphysin and epsin contain a second, distinct sequence that is also capable of binding to clathrin directly [30].
• Bin2 formed a stable complex in cells with Bin1, but not with amphiphysin, in a BAR domain-dependent manner [31].
• Finally, transient overexpression of the specific dominant-negative inhibitors of clathrin-mediated endocytosis, the SH3 domain of amphiphysin and the C-terminal domain of AP180, potently inhibited internalization of HRV2 [32].

Analytical, diagnostic and therapeutic context of AMPH

• These in vivo microdialysis results indicate that ontogenetic co-exposure to cadmium, and ethanol produces a long-lived suppressive effect on HAL-evoked DA release and a long-lived enhancing effect on AMPH-evoked DA release in rat striatum [33].
• The biological half-time of AMPH in the blood was reduced after premedication with CPH 5 mg/kg [34].
• Confocal immunofluorescence revealed that cells transfected with the amphiphysin SH3 domain showed a potent blockade in receptor-mediated endocytosis [35].
• At least 9 different subtypes of the isoform with 50-60% amino acid identity to the human amphiphysin were identified by a conventional library screening and PCR amplification of cDNA libraries [36].
• Reverse transcriptase-polymerase chain reaction demonstrated expression of amphiphysin in 8 of 10 small-cell lung carcinomas and in 5 of 14 breast carcinomas [37].

References