Biology subjects

Hashimi, H.

Publications and source records attributed to Hashimi, H..

3 recordsLinked to original sources

bioRxiv2021

Trypanosome morphogenesis involves recruitment of a pleckstrin homology domain protein by an orphan kinesin to the microtubule quartet

Kinesins are motor proteins found in all eukaryotic lineages that move along microtubules to mediate cellular processes such as mitosis and intracellular transport. In trypanosomatids, the kinesin superfamily has undergone a prominent expansion, resulting in one of the most diverse kinesin repertoires that includes the two kinetoplastid-restricted families X1 and X2. Here, we characterize in Trypanosoma brucei TbKifX2A, an orphaned X2 kinesin. TbKifX2A tightly interacts with TbPH1, a kinesin-like protein with a likely inactive motor domain, a rarely reported occurrence. Both TbKifX2A and TbPH1 localize to the microtubule quartet (MtQ), a characteristic but poorly understood cytoskeletal structure that wraps around the flagellar pocket as it extends to the cell body anterior. The proximal proteome of TbPH1 revealed two other interacting proteins, the flagellar pocket protein FP45 and intriguingly another X2 kinesin, TbKifX2C. Simultaneous ablation of TbKifX2A/TbPH1 results in the depletion of FP45 and TbKifX2C and also an expansion of the flagellar pocket, among other morphological defects. TbKifX2A is the first motor protein to be localized to the MtQ. The observation that TbKifX2C also associates with the MtQ suggests that the X2 kinesin family may have co-evolved with the MtQ, both kinetoplastid-specific traits.

molecular biology↗

bioRxiv2021

MICOS and F1FO-ATP synthase crosstalk is a fundamental property of mitochondrial cristae

Mitochondrial cristae are polymorphic invaginations of the inner membrane that are the fabric of cellular respiration. Both the Mitochondrial Contact Site and Cristae Organization System (MICOS) and the FOF1-ATP synthase are vital for sculpting cristae by opposing membrane bending forces. While MICOS promotes negative curvature at cristae junctions, dimeric FOF1- ATP synthase is crucial for positive curvature at cristae rims. Crosstalk between these two complexes has been observed in bakers yeast, the model organism of the Opisthokonta supergroup. Here, we report that this property is conserved in Trypanosoma brucei, a member of the Discoba supergroup that separated from Opisthokonta [~]2 billion years ago. Specifically, one of the paralogs of the core MICOS subunit Mic10 interacts with dimeric F1FO-ATP synthase, whereas the other core Mic60 subunit has a counteractive effect on F1FO- ATP synthase oligomerization. This is evocative of the nature of MICOS-F1FO-ATP synthase crosstalk in yeast, which is remarkable given the diversification these two complexes have undergone during almost 2 eons of independent evolution. Furthermore, we identified a highly diverged trypanosome homolog of subunit e, which is essential for the stability of F1FO-ATP synthase dimers in yeast. Just like subunit e, it is preferentially associated with dimers, interacts with Mic10 and its silencing results in severe defects to cristae and disintegration of F1FO-ATP synthase dimers. Our findings indicate that crosstalk between MICOS and dimeric F1FO-ATP synthase is a fundamental property impacting cristae shape throughout eukaryotes. ImportanceMitochondria have undergone profound diversification in separate lineages that have radiated since the last common ancestor of eukaryotes some eons ago. Most eukaryotes are unicellular protists, including etiological agents of infectious diseases like Trypanosoma brucei. Thus, the study of a broad range of protists can reveal fundamental features shared by all eukaryotes and lineage-specific innovations. Here we report that two different protein complexes, MICOS and F1FO-ATP synthase, known to affect mitochondrial architecture, undergo crosstalk in T. brucei, just as in bakers yeast. This is remarkable considering that these complexes have otherwise undergone many changes during their almost two billion years of independent evolution. Thus, this crosstalk is a fundamental property needed to maintain proper mitochondrial structure even if the constituent players considerably diverged.

cell biology↗

bioRxiv2021

Mammalian adipogenesis regulators (Aregs) exhibit robust non- and anti-adipogenic properties that arise with age and involve retinoic acid signalling

Adipose stem and precursor cells (ASPCs) give rise to adipocytes and determine the composition and plasticity of adipose tissue. Recently, several studies have demonstrated that ASPCs partition into at least three distinct cell subpopulations: Dpp4+ stem-like cells, Aoc3+ pre-adipocyte-like cells, and the enigmatic CD142+ cells. A great challenge now is to functionally characterize these distinct ASPC populations. Here, we focus on CD142+ ASPCs since discrepant properties have been assigned to this subpopulation, from adipogenic to non- and even anti-adipogenic. To address these inconsistencies, we comprehensively characterized mammalian subcutaneous CD142+ ASPCs across various sampling conditions. Our findings demonstrate that CD142+ ASPCs exhibit high molecular and phenotypic robustness, firmly supporting their non- and anti-adipogenic properties. However, these properties emerge in an age-dependent manner, revealing surprising temporal CD142+ ASPC behavioural alterations. Finally, using multi-omic and functional assays, we show that the inhibitory nature of these adipogenesis-regulatory CD142+ ASPCs (Aregs) is driven by specifically expressed secretory factors that cooperate with the retinoic acid signalling pathway to transform the adipogenic state of CD142- ASPCs into a non-adipogenic, Areg-like one.

cell biology↗