Although signal-transducing adaptor protein-2 (STAP-2) acts in certain immune responses, its role in B cell receptor (BCR)-mediated signals remains unknown. In this study, we have revealed that BCR-mediated signals, cytokine production and antibody production were increased in STAP-2 knockout (KO) mice compared with wild-type (WT) mice. Phosphorylation of tyrosine-protein kinase LYN Y508 was reduced in STAP-2 KO B cells after BCR stimulation. Mechanistic analysis revealed that STAP-2 directly binds to LYN, dependently of STAP-2 Y250 phosphorylation by LYN. Furthermore, phosphorylation of STAP-2 enhanced interactions between LYN and tyrosine-protein kinase CSK, resulting in enhanced CSK-mediated LYN Y508 phosphorylation. These results suggest that STAP-2 is crucial for controlling BCR-mediated signals and antibody production by enhanced CSK-mediated feedback regulation of LYN.

Ovarian fibrosis is a reproduction obstacle leading to female infertility in vertebrates, but the cause underlying the cellular events is unclear. Here, we found that the small adaptor protein SH3-domain-binding glutamate-rich protein like (Sh3bgrl) plays an important role in female reproduction in zebrafish. Two sh3bgrl mutant alleles that result in sh3bgrl depletion contribute to female spawning inability. Comparative transcriptome analysis revealed that sh3bgrl knockout mechanistically causes the upregulation of genes associated with extracellular matrix (ECM) and fiber generation in the zebrafish ovary. Consequently, extra ECM or fibers accumulate and are deposited in the ovary, resulting in eventual spawning inability. Our findings thus provide insights into understanding the underlying mechanism of infertility by ovarian fibrosis and provide a novel and valuable model to study female reproduction abnormality.

Grimontia hollisae collagenase (Ghcol) consists of 767 amino acid residues with a single catalytic domain containing the zinc-binding motif H492 EYVH496 . The crystal structure of Ghcol in complex with its substrate (Gly-Pro-hydroxyproline-Gly-Pro-hydroxyproline) and site-directed mutagenesis of active-site Tyr residues revealed the catalytic mechanism: Glu493 functions as an acid and base catalyst while Tyr564 stabilizes the tetrahedral complex in the transition state.

Chlorogenic acid esterases (ChlEs) are a useful class of enzymes that hydrolyze chlorogenic acid (CGA) into caffeic and quinic acid. ChlEs can break down CGA in foods to improve their sensory properties and release caffeic acid in the digestive system to improve the absorption of bioactive compounds. This work presents the structure, molecular dynamics, and biochemical characterization of a ChlE from Lactobacillus helveticus (Lh). Molecular dynamics simulations suggest that substrate access to the active site of LhChlE is modulated by two hairpin loops above the active site. Docking simulations and mutational analysis suggest that two residues within the loops, Gln145 and Lys164 , are important for CGA binding. Lys164 provides a slight substrate preference for CGA, whereas Gln145 is required for efficient turnover. This work is the first to examine the dynamics of a bacterial ChlE and provides insights on the substrate binding preference and turnover in this type of enzyme.

Nuclear pore complexes (NPCs) play a critical role in maintaining the equilibrium between the nucleus and cytoplasm, enabling bidirectional transport across the nuclear envelope, and are essential for proper nuclear organization and gene regulation. Perturbations in the regulatory mechanisms governing NPCs and nuclear envelope homeostasis have been implicated in the pathogenesis of several neurodegenerative diseases. The ESCRT-III pathway emerges as a critical player in the surveillance and preservation of well-assembled, functional NPCs, as well as nuclear envelope sealing. Recent studies have provided insights into the involvement of nuclear ESCRT-III in the selective reduction of specific nucleoporins associated with neurodegenerative pathologies. Thus, maintaining quality control of the nuclear envelope and NPCs represents a pivotal element in the pathological cascade leading to neurodegenerative diseases. This review describes the constituents of the nuclear-cytoplasmic transport machinery, encompassing the nuclear envelope, NPC, and ESCRT proteins, and how their structural and functional alterations contribute to the development of neurodegenerative diseases.