For our new Microtubules and Mitosis Journal Club on April 25, members of the Drubin/Barnes Lab, Eva Nogales Lab, and Ahmet Yildiz Lab discussed the following paper, selected by Nate Krefman:
Here’s the story of a lovely lady.
Who studied what a microtubule’s for.
All her group loves mitosis, like Georjana,
And kinetochores.
Here’s the story of a PI named David,
Who was interested in actin in live cells,
And his group mapped endocytosis dynamics,
Yet they were by themselves.
After their post-docs, where the lady met this fellow,
And named a protein complex DAM instead of DARN,
They knew their groups must form one laboratory.
That’s the way our lab became the Drubin/Barnes!
The Drubin/Barnes!
Centromeres (CB-mCherry) and chromosomes (YFP emission) for a single time point. (bottom) Color-coded YFP/CFP emission ratio at different time points. The timestamp (minutes and seconds) is relative to ZM washout at t = 0. Bar, 5 µm.
Scatter plot of correlation coefficients comparing GI profiles for Sp versus Sc. Highlighted examples of pairwise relationships that are correlated in Sp but not Sc are listed below the scatter plot. Bold indicates functional relationships explored in this study. See Table S1 for additional examples of correlated pairwise relationships conserved between Sp and Sc (green), and pairwise relationships that are correlated in Sc but not Sp (cyan) or Sp but not Sc (red).
Yidi Sun‘s new paper is out now as an electronic publication ahead of print in the journal Molecular Biology of the Cell. Congratulations to Yidi on her great work! The abstract is below. The PDF can be downloaded from MBoC here.
Sphingoid intermediates accumulate in response to a variety of stresses, including heat, and trigger cellular responses. However, the mechanism by which stress affects sphingolipid biosynthesis has yet to be identified. Recent studies in yeast suggested that sphingolipid biosynthesis is regulated through phosphorylation of the Orm proteins, which in humans are potential risk factors for childhood asthma. Here, we demonstrate that Orm phosphorylation status is highly responsive to sphingoid bases. We also demonstrate by monitoring temporal changes in Orm phosphorylation and sphingoid base production in cells inhibited for Ypk1 protein kinase activity, that Ypk1 transmits heat stress signals to the sphingolipid biosynthesis pathway via Orm phosphorylation. Our data indicate that heat-induced sphingolipid biosynthesis in turn triggers Orm protein dephosphorylation, making the induction transient. We identified Cdc55-PP2A (protein phosphatase 2A) as a key phosphatase that counteracts Ypk1 activity in Orm mediated sphingolipid biosynthesis regulation. In total, our study reveals a mechanism through which the conserved Pkh-Ypk kinase cascade and Cdc55-PP2A facilitate rapid, transient sphingolipid production in response to heat stress through Orm protein phosphoregulation. We propose that this mechanism serves as the basis for how Orm phosphoregulation controls sphingolipid biosynthesis in response to stress in a kinetically coupled manner.
A feedback regulation pathway in which Orm protein phosphorylation dynamics rapidly and precisely regulate sphingolipid biosynthesis in response to heat stress. See the text for a description.