Nature sub-journal: Biomacromolecular condensed matter regulates cell fate plasticity

On the 20th, the reporter learned from the University of Science and Technology of China that the joint team of Yao Xuebiao and Liu Xing, the key laboratory of cell dynamics of the Ministry of Education, elucidated the physicochemical mechanism of EB1 protein phase separation to regulate spindle dynamics and cell division fate decision, and took an important step
towards the analysis of the theoretical research on the regulation of cell fate plasticity by biomacromolecule condensed matter.
The research results were published in
the international academic journal Nature Cell Biology on December 20, Beijing time.

The cell is the smallest functional unit of life activities, and the cytoskeleton is the material basis of its compartmentalization, which is involved in cell growth, cell morphology, intercellular information exchange and the fate plasticity
of the extracellular microenvironment in which cells selectively respond.
Foreign scholars have discovered EB1
, an important regulatory protein of APC, when analyzing the functional susceptibility of APC mutants of familial rectal cancer genes.
However, how EB1 recruits numerous APC-like proteins (the human genome shows about 1,000 SxIP-containing motifs) to bind to dynamically changing β-tubulin has been an unanswered question
in cell biology, biophysics, and molecular pathology.

In 2009, the cell dynamics research team of the University of Science and Technology of China discovered and cloned a novel EB1-binding protein TIP150
when analyzing the microtubule dynamics mechanism of cell division.
TIP150 contains the typical EB1-binding protein motif SxIP, responsible for recruiting the microtubule depolymerase MCAK, which forms catalytic compartments
at the positive end of the dynamically assembled microtubule.
On this basis, the research team discovered the function
of basic amino acids in flexible regions in EB1 dimmerization and regulation of microtubule dynamics by using ultra-high-resolution microscopy imaging and fluorescent protein complementarity strategies of photosensitive localization of living cells.
Using multi-color single-molecule analysis, unnatural amino acid embedding and three-dimensional organoid multi-dimensional imaging, the joint team revealed the dynamic regulation mechanism of dynamic crotonylation modification and microtubule binding of lysine at position 66 of EB1, and its mechanism on the directional stability of cell division spindles
.

The researchers discovered the droplet characterization of EB1 protein in the dynamic microtubule tracking process of living cells, and used gene editing, physicochemistry to simulate the abundance and spacing of basic amino acids, combined with ultra-high-resolution imaging, revealed the phase separation characteristics and condensed matter basis of EB1 protein, and analyzed the positive end tracking function
of phase separation driving EB1 protein.

So far, the joint team has elucidated the physicochemical mechanism of EB1 protein phase separation regulating spindle microtubule plasticity, which has taken an important step
towards the analysis of the theoretical research on the regulation of cell fate plasticity by condensed matter of biological macromolecules.