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Gammoh, N.

Publications and source records attributed to Gammoh, N..

3 recordsLinked to original sources

Mapping the pathway for protein secretion in the secondary endosymbiotic alga Nannochloropsis oceanica

Microalgae are key primary producers in marine ecosystems, and their interactions with the surrounding environment rely on the secretion of intracellular metabolites and macromolecules, particularly proteins, supporting essential functions such as nutrient acquisition, environmental sensing and biotic interactions. Most abundant and ecologically relevant seawater algae are secondary endosymbionts, where multiple endosymbiotic events extensively reshaped plastids and intracellular membrane systems, requiring adaptation of protein trafficking mechanisms. This study presents the identification of signal peptides that direct protein secretion in the seawater microalga Nannochloropsis oceanica. Their expression in frame with a fluorescent tag enabled to reconstruct the protein secretion pathway in this organism. Proteins channelled for export are first targeted to the periplastidial compartment, an exclusive structure of secondary endosymbiotic algae, that acts as hub for protein trafficking. Subsequently, vesicle-mediated transport directs proteins through the endoplasmic reticulum into the periplasmic space between the cell membrane and the cell wall, from where they are released upon cell division. These findings reveal an evolutionarily remodeled protein secretion pathway, in which host- and endosymbiont-derived trafficking mechanisms merged into an integrated functional system. Significance StatementThe most abundant and ecologically relevant marine algae are secondary endosymbionts whose evolution required extensive re-adaptation of multiple cellular processes. Among them, protein secretion is essential for the interaction with external environment, and required specific re-shaping to the increased cellular complexity associated with endosymbiosis. This work uncovers protein secretory pathway in the secondary endosymbiont seawater alga Nannochloropsis oceanica showing that is does not follow a direct route, but proteins are first accumulated in the periplastidial compartment, a unique structure derived from its endosymbiotic history, before being directed for secretion. The final pathway integrated components derived from both the host and endosymbiont, highlighting how evolution was able to merge different biological modules to build an integrated and functional system.

plant biology↗

Depletion of BBSome Subunits Alters Receptor Endocytosis and Promotes EMT via TGF-β Signaling

Background: Ciliopathies are genetic disorders caused by defects in the structure or function of the cilia and their related structures. Bardet-Biedl syndrome (BBS) is a complex ciliopathy with varied symptoms, probably due to altered membrane receptor signalling pathways. Methods: We investigated the role of BBS1 and BBS4 gene deficiencies in retinal epithelial cells using surface membrane proteomics, co-immunoprecipitation, AlphaFold structural modelling, endocytic trafficking colocalization assays, autophagy flux analysis, and epithelial-to-mesenchymal transition (EMT) functional assays including migration and wound healing. Results: Deficiencies in these BBSome components led to shorter cilia and disrupted receptor endocytosis, with accumulation of TGF-{beta}-pathway and EMT-associated proteins on the plasma membrane of BBS1 KO cells. Co-immunoprecipitation and AlphaFold structural modelling indicated that neither BBS1 nor BBS4 forms stable physical complexes with core endocytic components (EEA1, RAB11, RAB7, LAMP2), suggesting an indirect mechanism. BBS1 KO cells showed sustained TGFBR1 recycling, low basal autophagic flux that increases upon TGF-{beta} stimulation, and the most pronounced mesenchymal phenotype. BBS4 KO cells showed reduced receptor recycling, elevated basal autophagic flux that declines upon stimulation, and the strongest canonical TGF-{beta}/SMAD activation with reduced non-canonical ERK1/2 signalling. Conclusions: Increased EMT markers and enhanced migration in BBS1 KO cells highlight the role of BBSome-dependent receptor trafficking as a potential therapeutic target for retinal degeneration in BBS. The divergent autophagic and signalling phenotypes between BBS1 and BBS4 KO reveal subunit-specific contributions to TGF-{beta} pathway dysregulation.

molecular biology↗

Trichoplein controls endothelial cell function by regulating autophagy

Autophagy is an essential cellular quality control process that emerged critical for vascular homeostasis. Here we describe, the role for Trichoplein (TCHP) protein in linking autophagy with endothelial cells (ECs) function. The depletion of TCHP in ECs impairs migration and sprouting. TCHP directly binds PCM1, to regulate degradation of GABARAP, thus leading to a defective autophagy. Mechanistically, TCHP is indispensable for autophagosome maturation and its depletion resulted in the accumulation of SQSTM1/p62 (p62) and unfolded protein aggregates in ECs. The latter process is coupled to TCHP-mediated NF-kB activation. Of note, low levels of TCHP and high p62 levels were detected in primary ECs from patients with coronary artery disease. In addition, Tchp knock-out mice showed accumulation of p62 in the heart and cardiac vessels and reduced cardiac vascularization. Here, we reveal an autophagy-mediated mechanism for TCHP down-regulation, which poses a plausible target for regulation of endothelial function.

molecular biology↗