Centronuclear Myopathy Caused by Defective Membrane Remodelling of Dynamin 2 and BIN1 Variants

Centronuclear myopathy (CNM) is a congenital myopathy characterised by centralised nuclei in skeletal myofibers. T-tubules, sarcolemmal invaginations required for excitation-contraction coupling, are disorganised in the skeletal muscles of CNM patients. Previous studies showed that various endocytic proteins are involved in T-tubule biogenesis and their dysfunction is tightly associated with CNM pathogenesis. DNM2 and BIN1 are two causative genes for CNM that encode essential membrane remodelling proteins in endocytosis, dynamin 2 and BIN1, respectively. In this review, we overview the functions of dynamin 2 and BIN1 in T-tubule biogenesis and discuss how their dysfunction in membrane remodelling leads to CNM pathogenesis

Nucleation process of the 2011 northern Nagano earthquake from nearby seismic observations

東北地方太平洋沖地震後に日本全国で発生した誘発地震のメカニズムを解析 --稠密地震観測網で捉えられた長野県北部の地震の前駆過程--. 京都大学プレスリリース. 2021-04-19.High-density seismic network detected inland earthquake precursors. 京都大学プレスリリース. 2021-05-10.The 2011 magnitude (M) 9.0 Tohoku-oki earthquake was followed by seismicity activation in inland areas throughout Japan. An outstanding case is the M6.2 Northern Nagano earthquake, central Japan, occurred 13-h after the megathrust event, approximately 400 km away from its epicenter. The physical processes relating the occurrence of megathrust earthquakes and subsequent activation of relatively large inland earthquakes are not well understood. Here we use waveform data of a dense local seismic network to reveal with an unprecedented resolution the complex mechanisms leading to the occurrence of the M6.2 earthquake. We show that previously undetected small earthquakes initiated along the Nagano earthquake source fault at relatively short times after the Tohoku-oki megathrust earthquake, and the local seismicity continued intermittently until the occurrence of the M6.2 event, being likely ‘modulated’ by the arrival of surface waves from large, remote aftershocks off-shore Tohoku. About 1-h before the Nagano earthquake, there was an acceleration of micro-seismicity migrating towards its hypocenter. Migration speeds indicate potential localized slow-slip, culminating with the occurrence of the large inland earthquake, with fluids playing a seismicity-activation role at a regional scale

Morphogenesis of the Inner Ear at Different Stages of Normal Human Development

This study examined the external morphology and morphometry of the human embryonic inner ear membranous labyrinth and documented its three-dimensional position in the developing embryo using phase-contrast X-ray computed tomography and magnetic resonance imaging. A total of 27 samples between Carnegie stage (CS) 17 and the postembryonic phase during trimester 1 (approximately 6-10 weeks after fertilization) were included. The otic vesicle elongated along the dorso-ventral axis and differentiated into the end lymphatic appendage and cochlear duct (CD) at CS 17. The spiral course of the CD began at CS18, with anterior and posterior semicircular ducts (SDs) forming prominent circles with a common crus. The spiral course of the CD comprised more than two turns at the postembryonic phase, at which time the height of the CD was evident. A linear increase was observed in the length of anterior, posterior, and lateral SDs, in that order, and the length of the CD increased exponentially over the course of development. Bending in the medial direction was observed between the cochlear and vestibular parts from the latero-caudal view, with the angle decreasing during development. The position of the inner ear was stable throughout the period of observation on the lateral to ventral side of the rhombencephalon, caudal to the pontine flexure, and adjacent to the auditory ganglia. The plane of the lateral semicircular canal was approximately 8.0°-14.6° with respect to the cranial caudal (z-)axis, indicating that the orientation of the inner ear changes during growth to adulthood

The chromosomal passenger complex controls the function of endosomal sorting complex required for transport-III Snf7 proteins during cytokinesis

Cytokinesis controls the proper segregation of nuclear and cytoplasmic materials at the end of cell division. The chromosomal passenger complex (CPC) has been proposed to monitor the final separation of the two daughter cells at the end of cytokinesis in order to prevent cell abscission in the presence of DNA at the cleavage site, but the precise molecular basis for this is unclear. Recent studies indicate that abscission could be mediated by the assembly of filaments comprising components of the endosomal sorting complex required for transport-III (ESCRT-III). Here, we show that the CPC subunit Borealin interacts directly with the Snf7 components of ESCRT-III in both Drosophila and human cells. Moreover, we find that the CPC's catalytic subunit, Aurora B kinase, phosphorylates one of the three human Snf7 paralogues—CHMP4C—in its C-terminal tail, a region known to regulate its ability to form polymers and associate with membranes. Phosphorylation at these sites appears essential for CHMP4C function because their mutation leads to cytokinesis defects. We propose that CPC controls abscission timing through inhibition of ESCRT-III Snf7 polymerization and membrane association using two concurrent mechanisms: interaction of its Borealin component with Snf7 proteins and phosphorylation of CHMP4C by Aurora B

Investigating the role of the Itoigawa-Shizuoka tectonic line towards the evolution of the Northern Fossa Magna rift basin

AbstractThe Itoigawa-Shizuoka tectonic line (ISTL) fault system is considered to have one of the highest probabilities for a major inland earthquake occurrence in the whole of Japan. It is a complex fault system with the dip directions of the local fault segments changing from north to south between an east-dipping low-angle thrust fault, a strike slip fault and a west-dipping thrust fault. The tectonic relations between the different parts of the fault system and the surrounding geological units are yet to be fully explained. This study aims to reveal the juncture of the northern and central parts of the ISTL and investigate its contribution towards the shaping of the Northern Fossa Magna rift basin. We conducted 3 deployments of 1 or 2 linear arrays of seismic stations across the central and northern ISTL regions and observed local micro-earthquakes for a period of 3 years. Each deployment recorded continuous waveform data for approximately 3 months. Using arrival times of 1193 local earthquakes, we jointly determined earthquake locations and a 3D velocity model, applying the tomography method. We were able to image the regional crustal structures from the surface to a depth of 20km with a spatial resolution of 5km. Subsequently, we used the obtained 3D velocity model to relocate the background local seismicity from 2003 to 2009. The juncture of the northern and central parts of the ISTL was well constrained by our results. The depth extension of the northern parts of the ISTL fault segments follows the bottom of the Miocene Northern Fossa Magna rift basin (NFM) and forms an east-dipping low-angle fault. In contrast, the central parts of the ISTL fault segments are estimated to lie along the eastern boundary of the Matsumoto basin forming an oblique strike slip fault (Fig. 1)

Interaction between Anillin and RacGAP50C connects the actomyosin contractile ring with spindle microtubules at the cell division site

Anillin, one of the first factors recruited to the cleavage site during cytokinesis, interacts with actin, myosin II and septins, and is essential for proper organization of the actomyosin contractile ring. We employed affinity-purification methodology coupled with mass spectrometry to identify Anillin-interacting molecules in Drosophila cells. We isolated several actin and myosin proteins, three of the five Drosophila septins and RacGAP50C (Tum), a component of the centralspindlin complex. Using drug and RNA interference (RNAi) treatments we established that F-actin is essential for Anillin cortical localization in prometaphase but not for its accumulation at the cleavage furrow after anaphase onset. Moreover, septins were not recruited to the cleavage site in cells in which Anillin was knocked down by RNAi, but localized to central-spindle microtubules, suggesting that septins travel along microtubules to interact with Anillin at the furrow. Finally, we demonstrate that RacGAP50C is necessary for Anillin accumulation at the furrow and that the two proteins colocalize in vivo and interact in vitro. Thus, in addition to its role in activating RhoA signalling, RacGAP50C also controls the proper assembly of the actomyosin ring by interacting with Anillin at the cleavage furrow

Interaction between Anillin and RacGAP50C connects the actomyosin contractile ring with spindle microtubules at the cell division site

Anillin, one of the first factors recruited to the cleavage site during cytokinesis, interacts with actin, myosin II and septins, and is essential for proper organization of the actomyosin contractile ring. We employed affinity-purification methodology coupled with mass spectrometry to identify Anillin-interacting molecules in Drosophila cells. We isolated several actin and myosin proteins, three of the five Drosophila septins and RacGAP50C (Tum), a component of the centralspindlin complex. Using drug and RNA interference (RNAi) treatments we established that F-actin is essential for Anillin cortical localization in prometaphase but not for its accumulation at the cleavage furrow after anaphase onset. Moreover, septins were not recruited to the cleavage site in cells in which Anillin was knocked down by RNAi, but localized to central-spindle microtubules, suggesting that septins travel along microtubules to interact with Anillin at the furrow. Finally, we demonstrate that RacGAP50C is necessary for Anillin accumulation at the furrow and that the two proteins colocalize in vivo and interact in vitro. Thus, in addition to its role in activating RhoA signalling, RacGAP50C also controls the proper assembly of the actomyosin ring by interacting with Anillin at the cleavage furrow