Rui Duan

Recent studies in Drosophila have implicated actin cytoskeletal remodeling in myoblast fusion, but the cellular mechanisms underlying this process remain poorly understood. Here we show that actin polymerization occurs in an asymmetric and cell type-specific manner between a muscle founder cell and a fusion-competent myoblast (FCM). In the FCM, a dense F-actin-enriched focus forms at the site of fusion, whereas a thin sheath of F-actin is induced along the apposing founder cell membrane. The FCM-specific actin focus invades the apposing founder cell with multiple finger-like protrusions, leading to the formation of a single-channel macro fusion pore between the two muscle cells. Two actin nucleation-promoting factors of the Arp2/3 complex, WASP and Scar, are required for the formation of the F-actin foci, whereas WASP but not Scar promotes efficient foci invasion. Our studies uncover a novel invasive podosome-like structure (PLS) in a developing tissue and reveal a previously unrecognized function of PLSs in facilitating cell membrane juxtaposition and fusion.

Cell-cell fusion is critical for the conception, development, and physiology of multicellular organisms. Although cellular fusogenic proteins and the actin cytoskeleton are implicated in cell-cell fusion, it remains unclear whether and how they coordinate to promote plasma membrane fusion. We reconstituted a high-efficiency, inducible cell fusion culture system in the normally nonfusing Drosophila S2R+ cells. Both fusogenic proteins and actin cytoskeletal rearrangements were necessary for cell fusion, and in combination they were sufficient to impart fusion competence. Localized actin polymerization triggered by specific cell-cell or cell-matrix adhesion molecules propelled invasive cell membrane protrusions, which in turn promoted fusogenic protein engagement and plasma membrane fusion. This de novo cell fusion culture system reveals a general role for actin-propelled invasive membrane protrusions in driving fusogenic protein engagement during cell-cell fusion.

Our findings indicate that HIIT ameliorates Alzheimer's disease-like pathology by regulating astrocyte phenotype and astrocyte phenotype-associated AQP4 polarization. These changes promote Aβ and p-tau clearance from the brain tissue through the glymphatic system and the kidney.

PURPOSE: This study aimed to examine the effects of swimming exercise pretreatment on a streptozotocin (STZ)-induced sporadic Alzheimer's disease (AD) rat model and provide an initial understanding of related molecular mechanisms. METHODS: Male 2.5-month-old Sprague-Dawley rats were divided into the following four groups: (a) control, (b) swim + vehicle, (c) STZ without swim, and (d) swim + STZ. The Barnes maze task and novel object recognition test were used to measure hippocampus-dependent spatial learning and working memory, respectively. Immunofluorescence staining, Western blot analysis, enzyme-linked immunosorbent assay (ELISA) analysis, and related assay kits were used to assess synaptic proteins, inflammatory cytokines, total antioxidant capacity, antioxidant enzymes, amyloid-beta production, and tau hyperphosphorylation. RESULTS: Behavioral tests revealed that exercise pretreatment could significantly inhibit STZ-induced cognitive dysfunction (P < 0.05). STZ animals displayed significant loss of presynaptic/postsynaptic markers in the hippocampal CA1 that was reversed by exercise pretreatment (P < 0.05). STZ rats also displayed increased reactive gliosis, release of proinflammatory cytokines, and oxidative damage, effects attenuated by preexercise (P < 0.05, between-treatment changes). Likewise, preexercise significantly induced protein expression (P < 0.001) and DNA-binding activity (P = 0.015) of Nrf2 and downstream antioxidant gene expression in the hippocampal CA1 region (P < 0.05). STZ rats had increased levels of amyloid-beta (1-42) and tau hyperphosphorylation that were significantly ameliorated by exercise (P < 0.05). Histological studies showed that exercise imparted substantial neuroprotection (P < 0.001), suppressing neuronal apoptosis-like cell death in the hippocampal CA1 compared with the STZ control group (P < 0.001). CONCLUSIONS: Exercise pretraining exerts multifactorial benefits on AD that support its use as a promising new therapeutic option for prevention of neurodegeneration in the elderly and/or AD population.