Biology subjects

Ali Moussa, H. Y.

Publications and source records attributed to Ali Moussa, H. Y..

3 recordsLinked to original sources

bioRxiv2025

Synaptotagmin-1 and complexin inhibit spontaneous vesicle fusion by masking PIP2, not by clamping SNARE assembly

Vesicle fusion underlies neurotransmitter release, enabling cellular communication. The rapid kinetics of vesicle fusion, tight docking to the plasma membrane, and coordination by multiple SNARE complexes suggest that SNARE complexes are already pre-assembled before fusion. Synaptotagmin-1 (Syt-1) and complexin (CPLX) have been proposed to clamp SNARE assembly and arrest fusion. However, these models are largely based on studies conducted under low ionic strength and structural analyses utilizing SNARE-Syt-1 chimera conjugates. We propose phosphatidylinositol 4,5-bisphosphate (PIP2) as a critical lipid catalyst that facilitates fusion through electrostatic dehydration. Here we show that neither the C2AB domain of Syt-1 nor CPLX-2 has clamping or inhibitory effect on SNARE assembly. Instead, the C2AB domain and CPLX-2 inhibit Ca2+-independent vesicle fusion by masking PIP2. Our data resolve the long-standing question of increased spontaneous neurotransmitter release in Syt-1 and CPLX knockout neurons, emphasizing PIP2 as an electrostatic lipid catalyst for fusion. One Sentence SummarySyt-1 and complexin inhibit spontaneous fusion by masking PIP2.

neuroscience↗

bioRxiv2024

Longitudinal cellular and humoral immune responses following Covid-19 BNT162b2-mRNA-based booster vaccination of craft and manual workers in Qatar.

IntroductionIn March 2020, the rapid spread of SARS-CoV-2 prompted global vaccination campaigns to mitigate COVID-19 disease severity and mortality. The 2-dose BNT162b2- mRNA vaccine effectively reduced infection and mortality rates, however, waning vaccine effectiveness necessitated the introduction of a third vaccine dose or booster. To assess the magnitude and longevity of booster-induced immunity, we conducted a longitudinal study of SARS-CoV-2 specific cellular and humoral immune responses among Qatars vulnerable craft and manual worker community. We also investigated the impact of prior naturally acquired immunity on booster vaccination efficacy. MethodsSeventy healthy participants were enrolled in the study, of whom half had prior SARS-CoV-2 infection. Blood samples were collected before and after booster vaccination to evaluate immune responses through SARS- CoV-2 specific ELISpots, IgG ELISA, neutralization assays, and flow cytometric immunophenotyping ResultsT cell analysis revealed increased Th1 cellular responses, marked by enhanced IFN-{gamma} release, in recently infected participants, which was further enhanced by booster vaccination for up to 6-months. Furthermore, booster vaccination stimulated cytotoxic T cell responses in infection-naive participants, characterized by granzyme B production. Both natural SARS-CoV-2 infection and booster vaccination induced robust and durable SARS-CoV-2 specific humoral immune responses, with high neutralizing antibody levels. Prior natural infection was also linked to an increased number of class- switched B cells prior to booster vaccination. ConclusionThese findings underscore the importance of booster vaccination in enhancing anti-viral immunity across both infection-naive and previously infected individuals, enhancing distinct arms of the anti-viral immune response and prolonging naturally acquired immunity.

immunology↗

bioRxiv2022

Deletion of TRPC6, an autism risk gene, induces hyperexcitability in cortical neurons derived from human pluripotent stem cells

Autism spectrum disorder (ASD) is a complex and heterogeneous neurodevelopmental disorder linked to numerous rare, inherited and arising de novo genetic variants. ASD often co-occurs with attention-deficit hyperactivity disorder and epilepsy, which are associated with hyperexcitability of neurons. However, the physiological and molecular mechanisms underlying hyperexcitability in ASD remain poorly understood. Transient receptor potential canonical-6 (TRPC6) is a Ca2+-permeable cation channel that regulates store-operated calcium entry (SOCE) and is a candidate risk gene for ASD. Using human pluripotent stem cell (hPSC)-derived cortical neurons, single cell calcium imaging, and electrophysiological recording, we show that TRPC6 knockout (KO) reduces SOCE signaling and leads to hyperexcitability of neurons by increasing action potential frequency and network burst frequency. Our data provide evidence that reduction of SOCE by TRPC6 KO results in neuronal hyperexcitability, which we hypothesize is an important contributor to the cellular pathophysiology underlying hyperactivity in some ASD.

neuroscience↗