bims-mecosi 2022-04-24 papers

Issue of 2022‒04‒24
five papers selected by
Verena Kohler

Traffic. 2022 Apr 22.

Arabidopsis synaptotagmin 1 mediates lipid transport in a lipid composition-dependent manner.

Tiantian Qian, Chenlu Li, Furong Liu, Kai Xu, Chun Wan, Yinghui Liu, Haijia Yu.

The endoplasmic reticulum (ER) - plasma membrane (PM) contact sites (EPCSs) are structurally conserved in eukaryotes. The Arabidopsis ER-anchored synaptotagmin 1 (SYT1), enriched in EPCSs, plays a critical role in plant abiotic stress tolerance. It has become clear that SYT1 interacts with PM to mediate ER-PM connectivity. However, whether SYT1 performs additional functions at EPCSs remains unknown. Here, we reported that SYT1 efficiently transfers phospholipids between membranes. The lipid transfer activity of SYT1 is highly dependent on PI(4,5)P2 , a signal lipid accumulated at the PM under abiotic stress. Mechanically, while SYT1 transfers lipids fundamentally through the synaptotagmin-like mitochondrial-lipid-binding protein (SMP) domain, the efficient lipid transport requires the C2A domain-mediated membrane tethering. Interestingly, we observed that Ca2+ could stimulate SYT1-mediated lipid transport. In addition to PI(4,5)P2 , the Ca2+ activation requires the phosphatidylserine, another negatively charged lipid on the opposed membrane. Together, our studies identified Arabidopsis SYT1 as a lipid transfer protein at EPCSs and demonstrated it takes conserved as well as divergent mechanisms with other extend-synaptotagmins. The critical role of lipid composition and Ca2+ reveals SYT1-mediated lipid transport is highly regulated by signals in response to abiotic stresses.

Keywords: SMP; endoplasmic reticulum; lipid transfer; membrane contact sites; plasma membrane; synaptotagmin

DOI: https://doi.org/10.1111/tra.12844

Biomolecules. 2022 Apr 12. pii: 567. [Epub ahead of print]12(4):

The Interplay of Microtubules with Mitochondria-ER Contact Sites (MERCs) in Glioblastoma.

Francesca Grespi, Caterina Vianello, Stefano Cagnin, Marta Giacomello, Agnese De Mario.

Gliomas are heterogeneous neoplasms, classified into grade I to IV according to their malignancy and the presence of specific histological/molecular hallmarks. The higher grade of glioma is known as glioblastoma (GB). Although progress has been made in surgical and radiation treatments, its clinical outcome is still unfavorable. The invasive properties of GB cells and glioma aggressiveness are linked to the reshaping of the cytoskeleton. Recent works suggest that the different susceptibility of GB cells to antitumor immune response is also associated with the extent and function of mitochondria-ER contact sites (MERCs). The presence of MERCs alterations could also explain the mitochondrial defects observed in GB models, including abnormalities of energy metabolism and disruption of apoptotic and calcium signaling. Based on this evidence, the question arises as to whether a MERCs-cytoskeleton crosstalk exists, and whether GB progression is linked to an altered cytoskeleton-MERCs interaction. To address this possibility, in this review we performed a meta-analysis to compare grade I and grade IV GB patients. From this preliminary analysis, we found that GB samples (grade IV) are characterized by altered expression of cytoskeletal and MERCs related genes. Among them, the cytoskeleton-associated protein 4 (CKAP4 or CLIMP-63) appears particularly interesting as it encodes a MERCs protein controlling the ER anchoring to microtubules (MTs). Although further in-depth analyses remain necessary, this perspective review may provide new hints to better understand GB molecular etiopathogenesis, by suggesting that cytoskeletal and MERCs alterations cooperate to exacerbate the cellular phenotype of high-grade GB and that MERCs players can be exploited as novel biomarkers/targets to enhance the current therapy for GB.

Keywords: MAMs; MERCs; cytoskeleton; gene expression; glioblastoma; glioblastoma invasion; glioma; microtubules; mitochondrial dynamics

DOI: https://doi.org/10.3390/biom12040567

Oxid Med Cell Longev. 2022 ;2022 2531458

Mitochondria-Endoplasmic Reticulum Contacts: The Promising Regulators in Diabetic Cardiomyopathy.

Yan Chen, Yanguo Xin, Yue Cheng, Xiaojing Liu.

Diabetic cardiomyopathy (DCM), as a serious complication of diabetes, causes structural and functional abnormalities of the heart and eventually progresses to heart failure. Currently, there is no specific treatment for DCM. Studies have proved that mitochondrial dysfunction and endoplasmic reticulum (ER) stress are key factors for the development and progression of DCM. The mitochondria-associated ER membranes (MAMs) are a unique domain formed by physical contacts between mitochondria and ER and mediate organelle communication. Under high glucose conditions, changes in the distance and composition of MAMs lead to abnormal intracellular signal transduction, which will affect the physiological function of MAMs, such as alter the Ca2+ homeostasis in cardiomyocytes, and lead to mitochondrial dysfunction and abnormal apoptosis. Therefore, the dysfunction of MAMs is closely related to the pathogenesis of DCM. In this review, we summarized the evidence for the role of MAMs in DCM and described that MAMs participated directly or indirectly in the regulation of the pathophysiological process of DCM via the regulation of Ca2+ signaling, mitochondrial dynamics, ER stress, autophagy, and inflammation. Finally, we discussed the clinical transformation prospects and technical limitations of MAMs-associated proteins (such as MFN2, FUNDC1, and GSK3β) as potential therapeutic targets for DCM.

DOI: https://doi.org/10.1155/2022/2531458

Biomolecules. 2022 Mar 23. pii: 488. [Epub ahead of print]12(4):

The Sarcoplasmic Reticulum of Skeletal Muscle Cells: A Labyrinth of Membrane Contact Sites.

Daniela Rossi, Enrico Pierantozzi, David Osamwonuyi Amadsun, Sara Buonocore, Egidio Maria Rubino, Vincenzo Sorrentino.

The sarcoplasmic reticulum of skeletal muscle cells is a highly ordered structure consisting of an intricate network of tubules and cisternae specialized for regulating Ca2+ homeostasis in the context of muscle contraction. The sarcoplasmic reticulum contains several proteins, some of which support Ca2+ storage and release, while others regulate the formation and maintenance of this highly convoluted organelle and mediate the interaction with other components of the muscle fiber. In this review, some of the main issues concerning the biology of the sarcoplasmic reticulum will be described and discussed; particular attention will be addressed to the structure and function of the two domains of the sarcoplasmic reticulum supporting the excitation-contraction coupling and Ca2+-uptake mechanisms.

Keywords: Ca2+; intracellular membrane; muscle; myopathy

DOI: https://doi.org/10.3390/biom12040488

Life Sci Alliance. 2022 Aug;pii: e202201430. [Epub ahead of print]5(8):

Tricalbin proteins regulate plasma membrane phospholipid homeostasis.

Ffion B Thomas, Deike J Omnus, Jakob M Bader, Gary Hc Chung, Nozomu Kono, Christopher J Stefan.

The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the ER and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain incomplete. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also control the PM targeting of the known phosphatidylserine effector Pkc1 upon heat-induced stress. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We propose that phospholipid regulation is an ancient essential function of E-Syt family members required for PM integrity.

DOI: https://doi.org/10.26508/lsa.202201430