The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer.

Camilli, Pietro De; Thomas, Annette; Cofiell, Roxanne; Folli, Franco; Lichte, Beate; Piccolo, G.; Meinck, H.-M.; Austoni, M; Fassetta, G; Bottazzo, G. F.; Bates, David; Cartlidge, N.E.F.; Solimena, Michele; Kilimann, Manfred W.

doi:10.1084/jem.178.6.2219

Cited by 301 publications

(198 citation statements)

References 27 publications

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“…Unlike amphiphysin, it has a broad expression in several mouse tissues and may be seen as a ubiquitous amphiphysin homologue. In patients with stiff-man syndrome associated with breast cancer (15), it is a potential target outside the brain for anti-amphiphysin autoantibodies. From one mouse tissue to the other, the expression of amphiphysin 2 seems to be dependent on multiple transcripts, generated either by different sites of initiation/polyadenylation or by alternative splicing.…”

Section: Resultsmentioning

confidence: 99%

A New Member of the Amphiphysin Family Connecting Endocytosis and Signal Transduction Pathways

Leprince¹,

Romero²,

Cussac³

et al. 1997

Journal of Biological Chemistry

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Src homology 3 (SH3) domains are conserved modules which participate in protein interaction by recognizing proline-rich motifs on target molecules. To identify new SH3-containing proteins, we performed a two-hybrid screen with a proline-rich region of human SOS-1. One of the specific SOS-1 interacting clones that were isolated from a mouse brain cDNA library defines a new protein that was named amphiphysin 2 because of its homology to the previously reported amphiphysin. Amphiphysin 2 is expressed in a number of mouse tissues through multiple RNA transcripts. Here, we report the amino acid sequence of a brain form of amphiphysin 2 (BRAMP2) encoded by a 2.5-kilobase mRNA. BRAMP2 associates in vitro with elements of the endocytosis machinery such as ␣-adaptin and dynamin. On a biosensor surface, the BRAMP2/dynamin interaction appeared to be direct and partly dependent on a proline-rich sequence of dynamin. Association with dynamin was also observed in PC12 cells after cell stimulation with nerve growth factor, suggesting that amphiphysin 2 may be connected to receptor-dependent signaling pathways. This hypothesis is strengthened by the ability of BRAMP2 to interact with the p21 ras exchange factor SOS, in vitro, as a possible point of interconnection between the endocytic and signaling pathways.A limited set of protein modules mediates molecular interactions and underlies the diversity of intracellular signaling pathways. Among these modules, Src homology 3 (SH3) 1 domains were first identified as non-catalytic regions of 55-70 AA, present in signaling and cytoskeletal proteins (1). A common feature of SH3 domains is their ability to bind proline-rich sequences on target molecules. A SH3 domain is composed of a hydrophobic binding pocket with finely positioned aromatic residues and charged loops outside of this pocket that determine the specificity of the interaction with proline-rich motifs. Phage display or peptide library screenings with individual SH3 domains demonstrated the absence of a strict exclusivity for SH3 and proline-rich partners (2, 3). This feature may be the basis for the identification of new SH3-containing proteins.Human SOS-1 C terminus contains a multitude of intermingled proline-rich motifs. It was used as a "pseudo-degenerated" bait in search for new SH3 domains in a two-hybrid screen. Several SH3 domains were isolated, and one of them allowed us to identify a new protein, homologous to, but different from, amphiphysin (4), that was named amphiphysin 2. Amphiphysin is a strictly neuronal protein that plays a crucial role in the endocytosis of synaptic vesicles (5). A current hypothesis suggests that a ubiquitous homologue involved in general endocytosis should exist. We show here that this hypothesis is correct and incomplete. Amphiphysin 2 is expressed under several forms: a 2.0-kb transcript which is expressed almost ubiquitously and a 2.5-kb transcript that is brain-specific. The latter form was further characterized in vitro and in vivo. We show that the brain form of amphiphysin 2 (BRA...

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Section: Resultsmentioning

confidence: 99%

A New Member of the Amphiphysin Family Connecting Endocytosis and Signal Transduction Pathways

Leprince¹,

Romero²,

Cussac³

et al. 1997

Journal of Biological Chemistry

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“…Pain, which is localized in the areas in which rigidity is observed, is persistent and worsening of pain might sometimes be the first symptom (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). Pain that is localized in the low back is associated with an increased lumbar lordosis and concomitant muscle spasms because of paraspinal muscle rigidity.…”

Section: Discussionmentioning

confidence: 99%

“…Five percent of patients have been reported to have the paraneoplastic condition (1,3,6,8). In some cases that develop with neoplasms, such as breast cancer, anti-amphiphiles or anti-gephyrin autoantibody positivity has been reported (9,10).…”

Section: Introductionmentioning

confidence: 99%

A Stiff Person Case Admitted Phsysical Medicine and Rehabilitation Outpatient Clinic with Low Back Pain

Karaoğlan¹,

Ote²,

Koseoglu³

et al. 2015

Turk J Phys Med Rehab

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Stiff-Person Syndrome (SPS) is a rare disorder that is characterized by stiffness and rigidity of the axial, abdominal, and extremity muscles. It is associated with several autoimmune diseases or paraneoplastic conditions. We report a case of SPS with Hashimoto's thyroiditis who complained of low back pain. Her physical examination was remarkable in that her abdominal and axial muscles were firm to palpation, and she had hyperlordosis of the spine. Active range of motion of the spine was limited, and she had a robotic gait. Electromyography demonstrated continuous motor unit activity in the agonist and antagonist muscles. Diagnosis of SPS was confirmed because antiglutamic acid decarboxylase was present in the cerebrospinal fluid. She favorably responded to intravenous administration of immunoglobulin, diazepam, and baclofen and stretching, strengthening, and range of motion exercises.

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“…Antiamphiphysin antibodies, syndromically associated with stiff-person syndrome (De Camilli et al, 1993), have also been associated with myelopathy . Of a series of 63 patients with antiamphiphysin antibodies, 18 manifested evidence at some point during the course of their illness and in 6 the myelopathy was the only neurologic manifestation (one man with malignant melanoma and five women: three with breast cancer, one with small cell lung cancer, and one without detected tumor).…”

Section: Antiamphiphysin Autoantibodiesmentioning

confidence: 99%

Acute inflammatory myelopathies

Cree

2014

Handbook of Clinical Neurology

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The synaptic vesicle-associated protein amphiphysin is the 128-kD autoantigen of Stiff-Man syndrome with breast cancer.

Cited by 301 publications

References 27 publications

A New Member of the Amphiphysin Family Connecting Endocytosis and Signal Transduction Pathways

A New Member of the Amphiphysin Family Connecting Endocytosis and Signal Transduction Pathways

A Stiff Person Case Admitted Phsysical Medicine and Rehabilitation Outpatient Clinic with Low Back Pain

Acute inflammatory myelopathies

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