LAB-1 Targets PP1 and Restricts Aurora B Kinase upon Entrance into Meiosis to Promote Sister Chromatid Cohesion

Successful execution of the meiotic program depends on the timely establishment and removal of sister chromatid cohesion. LAB-1 has been proposed to act in the latter by preventing the premature removal of the meiosis-specific cohesin REC-8 at metaphase I in C. elegans, yet the mechanism and scope of LAB-1 function remained unknown. Here we identify an unexpected earlier role for LAB-1 in promoting the establishment of sister chromatid cohesion in prophase I. LAB-1 and REC-8 are both required for the chromosomal association of the cohesin complex subunit SMC-3. Depletion of lab-1 results in partial loss of sister chromatid cohesion in rec-8 and coh-4 coh-3 mutants and further enhanced chromatid dissociation in worms where all three kleisins are mutated. Moreover, lab-1 depletion results in increased Aurora B kinase (AIR-2) signals in early prophase I nuclei, coupled with a parallel decrease in signals for the PP1 homolog, GSP-2. Finally, LAB-1 directly interacts with GSP-1 and GSP-2. We propose that LAB-1 targets the PP1 homologs to the chromatin at the onset of meiosis I, thereby antagonizing AIR-2 and cooperating with the cohesin complex to promote sister chromatid association and normal progression of the meiotic program

Anatomical and functional study of the medial collateral ligament complex of the elbow

OBJETIVO: Realizar um estudo anatômico do ligamento colateral medial, um importante estabilizador do cotovelo, em diferentes graus de flexo-extensão do cotovelo. MÉTODOS: Foram dissecados 40 cotovelos para analisar o comportamento funcional das bandas anterior, posterior e transversa do ligamento nas manobras de estresse em valgo do cotovelo durante seu movimento de flexão e extensão em diferentes graus. Determinou-se dois grupos: no GPA foi seccionado, a banda posterior do ligamento, depois a cápsula articular e, por fim, a banda anterior; no GAP, a ordem de dissecação foi inversa. RESULTADOS: No GPA observou-se instabilidade somente na terceira etapa e a média de abertura foi maior entre 50&º e 70&º de flexão de cotovelo; no GAP, a instabilidade apareceu desde a primeira etapa e os graus de flexão com maior instabilidade foram nos mesmos do grupo A. CONCLUSÃO: A banda anterior do ligamento colateral medial do cotovelo é o mais importante estabilizador na instabilidade em valgo do cotovelo e sua atuação principal acontece entre 50º e 70º de flexão do cotovelo. Nível de evidência III, Estudo Diagnóstico - Investigação de um exame para diagnóstico

Anatomical And Functional Study Of The Medial Collateral Ligament Complex Of The Elbow.

To carry out an anatomical study of the medial collateral ligament, an important elbow stabilizer in different degrees of elbow flexion-extension. Forty elbows were dissected in order to analyze the functional behavior of the anterior, posterior and transverse ligament bands during valgus stress maneuvers of the elbow in different degrees of flexion and extension. Two groups were determined; in the group GPA the posterior band of the ligament was sectioned initially, then the articular capsule and finally the anterior band; in group GAP this order was reversed. Instability was observed in GPA only in the third stage, when there was a greater mean elbow's opening during the flexion (between 50° and 70°); in GAP, the instability was present since the first stage; the degrees of flexion with greater instability were the same as in group GPA. The anterior band of the medial collateral ligament of the elbow is the most important stabilizer of the elbow valgus instability, and its principal action occurs between 50° and 70° of elbow flexion. Level of Evidence III, Diagnostic Studies - Investigating a diagnostic test.20334-

Estudo anatômico e funcional do complexo ligamentar colateral medial do cotovelo Anatomical and functional study of the medial collateral ligament complex of the elbow

OBJETIVO: Realizar um estudo anatômico do ligamento colateral medial, um importante estabilizador do cotovelo, em diferentes graus de flexo-extensão do cotovelo. MÉTODOS: Foram dissecados 40 cotovelos para analisar o comportamento funcional das bandas anterior, posterior e transversa do ligamento nas manobras de estresse em valgo do cotovelo durante seu movimento de flexão e extensão em diferentes graus. Determinou-se dois grupos: no GPA foi seccionado, a banda posterior do ligamento, depois a cápsula articular e, por fim, a banda anterior; no GAP, a ordem de dissecação foi inversa. RESULTADOS: No GPA observou-se instabilidade somente na terceira etapa e a média de abertura foi maior entre 50&º e 70&º de flexão de cotovelo; no GAP, a instabilidade apareceu desde a primeira etapa e os graus de flexão com maior instabilidade foram nos mesmos do grupo A. CONCLUSÃO: A banda anterior do ligamento colateral medial do cotovelo é o mais importante estabilizador na instabilidade em valgo do cotovelo e sua atuação principal acontece entre 50º e 70º de flexão do cotovelo. Nível de evidência III, Estudo Diagnóstico - Investigação de um exame para diagnóstico.OBJECTIVE: To carry out an anatomical study of the medial collateral ligament, an important elbow stabilizer in different degrees of elbow flexion-extension. METHODS: Forty elbows were dissected in order to analyze the functional behavior of the anterior, posterior and transverse ligament bands during valgus stress maneuvers of the elbow in different degrees of flexion and extension. Two groups were determined; in the group GPA the posterior band of the ligament was sectioned initially, then the articular capsule and finally the anterior band; in group GAP this order was reversed. RESULTS: Instability was observed in GPA only in the third stage, when there was a greater mean elbow's opening during the flexion (between 50º and 70º); in GAP, the instability was present since the first stage; the degrees of flexion with greater instability were the same as in group GPA. CONCLUSION: The anterior band of the medial collateral ligament of the elbow is the most important stabilizer of the elbow valgus instability, and its principal action occurs between 50º and 70º of elbow flexion. Level of Evidence III, Diagnostic Studies - Investigating a diagnostic test

LAB-1 antagonizes the Aurora B kinase in C. elegans

The Shugoshin/Aurora circuitry that controls the timely release of cohesins from sister chromatids in meiosis and mitosis is widely conserved among eukaryotes, although little is known about its function in organisms whose chromosomes lack a localized centromere. Here we show that Caenorhabditis elegans chromosomes rely on an alternative mechanism to protect meiotic cohesin that is shugoshin-independent and instead involves the activity of a new chromosome-associated protein named LAB-1 (Long Arm of the Bivalent). LAB-1 preserves meiotic sister chromatid cohesion by restricting the localization of the C. elegans Aurora B kinase, AIR-2, to the interface between homologs via the activity of the PP1/Glc7 phosphatase GSP-2. The localization of LAB-1 to chromosomes of dividing embryos and the suppression of mitotic-specific defects in air-2 mutant embryos with reduced LAB-1 activity support a global role of LAB-1 in antagonizing AIR-2 in both meiosis and mitosis. Although the localization of a GFP fusion and the analysis of mutants and RNAi-mediated knockdowns downplay a role for the C. elegans shugoshin protein in cohesin protection, shugoshin nevertheless helps to ensure the high fidelity of chromosome segregation at metaphase I. We propose that, in C. elegans, a LAB-1-mediated mechanism evolved to offset the challenges of providing protection against separase activity throughout a larger chromosome area

LAB-1 is required for homologous pairing.

<p>(A) High-magnification images of DAPI stained mid-pachytene nuclei (blue) hybridized with FISH probes targeting the pairing center region on chromosome I (red). Nuclei with either one, two, or three signals (foci) are depicted. Bars, 3 µM. (B) Diagram of a <i>C. elegans</i> germline indicating the position of the zones scored in the analysis of the progression of homologous pairing. (C, D) Graphs depicting the percentage of nuclei showing one, two, and three to four foci within each zone in control and <i>lab-1(RNAi)</i> gonads hybridized with FISH probes recognizing the chromosome I pairing center (C) and the X chromosome pairing center (D).</p