Biomedical subjects

M Filali

Publications and source records attributed to M Filali.

6 recordsLinked to original sources

PubMed1999

Monoclonal antibody specific to a subclass of polyproline-Arg motif provides evidence for the presence of an snRNA-free spliceosomal Sm protein complex in vivo: implications for molecular interactions involving proline-rich sequences of Sm B/B' proteins.

The human spliceosomal Sm B/B' proteins are essential for the biogenesis of the snRNP particles. B/B' proteins contain several clusters of the PPPPGM/IR sequence, which occurs within the C-terminus of Sm B/B'. This sequence is very similar to the PPPPPGHR sequence of the cytoplasmic tail of the CD2 receptor and closely resembles the class II of SH3 ligands, suggesting a similarly important role. We report that a monoclonal antibody (3E10) against the PPPPPGHR sequence recognizes spliceosomal Sm B/B' proteins. Proteins that are specifically immunoprecipitated by 3E10 include Sm B, B', D1, D2, D3, E, F, and G. However, unlike Y12 and other anti-Sm immunoprecipitates, 3E10 immunoprecipitates appear to lack the U1 snRNP-specific proteins A and C and U snRNAs. These findings indicate that 3E10 recognizes a subset of Sm protein core and suggest the presence of snRNA-free Sm protein complex(es) in vivo. We propose that the epitope binding for 3E10 may become unaccessible upon interactions of Sm proteins and their subsequent incorporation into the core particles. The Sm proline-rich sequences may have an important role in mediating protein-protein interactions necessary for the proper snRNP core assembly or function, or both. To our knowledge, 3E10 is the first well characterized mAb specific for a subclass of polyproline-arg motif recognizing Sm B/B' and CD2 proteins. 3E10 antibody can be used to further characterize the nature of protein components in the snRNA-free Sm subcore protein complex(es) that are formed during the snRNP core assembly steps.

Amino Acid Sequence↗

PubMed1999

Identification of a type 6 protein ser/thr phosphatase regulated by interleukin-2 stimulation.

We have identified a 36 kD phosphoprotein that forms a complex with spliceosomal small nuclear ribonucleoproteins in lymphocyte extracts. This 36 kD protein is differentially phosphorylated in transformed human lymphoid cell lines and is regulated by IL-2 in peripheral blood T cells. We purified the 36 kD protein from human lymphocytes by employing a combination of immuno-affinity chromatography and preparative two-dimensional gel electrophoresis. Internal amino acid sequence analysis of the purified protein yielded two peptides that had perfect matches with sequences in the human protein serine/threonine phosphatase 6 (PP6). Using degenerate primers corresponding to the peptides, we obtained from a human T lymphocyte cDNA library a DNA fragment whose sequence is homologous to an EST cDNA clone (R05547). The predicted amino acid sequence of this clone showed over 98% sequence identity to human PP6. The identification of an IL-2 regulated type 6 protein serine/threonine phosphatase in lymphocytes was further substantiated by immunoblotting with anti-peptide antibodies. These findings suggest that PP6 is a component of a signaling pathway regulating cell cycle progression in response to IL-2 receptor stimulation.

Amino Acid Sequence↗

PubMed1996

Sensorimotor learning in three cerebellar mutant mice.

Cerebellar damage occurs during developmental stages in three mutant mice (staggerer, hot-foot, and lurcher), causing disturbances in posture and equilibrium. During three tests of motor coordination, the performances of staggerer mutants was inferior to that of normal mice and did not improve with extended practice for up to 7 days of training. The sensorimotor performance of hot-foot mutants and of lurcher mutants was also lower than that of normal mice. Nevertheless, hot-foot mutants showed evidence of learning in two of the three tests and lurcher mutants in all three tests. Cerebellar atrophy in the latter two mutants did not prevent sensorimotor learning, but instead impaired their ability to reach the same level of performance as that of normal mice.

Animals↗

PubMed1996

Spontaneous alternation, motor activity, and spatial learning in hot-foot mutant mice.

Hot-foot mutant mice, characterized by defective innervation of Purkinje cells and an ataxic gait, were less active than normal mice in a T-maze. In spontaneous alternation testing with either single or multiple trials, hot-foot mutants, contrary to normal mice, did not alternate above chance. Moreover, the mutants had a higher number of errors and higher escape latencies in a water-filled Z-maze. These results indicate that in addition to motor coordination deficits, these cerebellar mutants have deficits in spatial learning and perseverate choices of maze arms.

Animals↗

PubMed1996

Spatial learning in a Z-maze by cerebellar mutant mice.

Two types of cerebellar mutant mice (staggerer and lurcher) were evaluated during 5-day acquisition of a spatial learning task in a Z-maze filled with water. Although the number of errors and escape latencies decreased in normal mice, the acquisition of the cerebellar mutants was impaired but not abolished. These results indicate that the cerebellum has a role in spatial learning. Mice with cerebellar dysfunction take a more indirect route toward a goal during the course of swimming, when ataxic symptoms are no longer in evidence.

Animals↗

PubMed1995

Rotorod sensorimotor learning in cerebellar mutant mice.

Lurcher mutant mice, characterized by degeneration of cerebellar granule and Purkinje cells, were compared to normal littermate controls in a rotorod test, consisting of a wheel turning at constant speed which required on the part of the animal postural adjustments in order to maintain equilibrium. Identical baseline rates for the two groups were assured by changing the speed and size of the rotating rod. Although both groups were able to learn the task, the fall latencies of normal mice exceeded those of lurchers. These results indicate that cerebellar cortical atrophy does not abolish this form of sensorimotor learning. However, brain-damaged animals are unable to reach the same level of performance as normal animals. In contrast to the results in lurcher mutants, no sensorimotor learning was displayed by hot-foot mutants and staggerer mutants.

Animals↗