Carlos A. Castaneda, assistant professor of biology, chemistry and interdisciplinary neuroscience, and Thuy Dao, a postdoctoral researcher in chemistry, have been working with ubiquitin, a tiny molecule that tags obsolete proteins in a cell. They recently found that ubiquitin eliminates droplets of Ubiquilin-2 (UBQLN2) in solution.
The discovery is noteworthy, Castaneda says, because UBQLN2 is a protein-encoding gene, mutations to which cause ALS and various types of dementia, such as frontotemporal dementia (FTD).
UBQLN2 - Motor - Inclusions - Patients - ALS
"UBQLN2 is found in motor neuron inclusions of patients with ALS," he says. "We show that UBQLN2 undergoes liquid-liquid phase separation, in which proteins coalesce into protein-rich droplets to form membraneless organelles in cells. Interestingly, dysfunction of membraneless organelle assembly and disassembly is emerging as a common pathogenic mechanism of ALS and other neurodegenerative disorders."
The ALS Association supports the duo's research, which in turn is the subject of a major paper in the journal Molecular Cell (Elsevier, 2018).
Authors - Brian - Martyniak - G'18 - PhD
Other authors include Brian Martyniak G'18, a second-year Ph.D. student in chemistry and biochemistry, who belongs to Castaneda's lab; members of J. Paul Taylor's research group from both St. Jude Children's Research Hospital and the Howard Hughes Medical Institute; and members of Heidi Hehnly's lab at SUNY Upstate Medical University.
"We want to understand the mechanisms that trigger motor neurons to degenerate in ALS," says Castaneda, the paper's lead contact. "It appears that pathological stress granules -- membraneless organelles thought to be formed by liquid-liquid phase separation of RNA-binding proteins -- trigger ALS and related disorders, leading to cell death."
Scientists - Cell - Stress - Proteins - RNA
Scientists know that when a eukaryotic cell is under stress, it causes certain proteins and RNA to form stress granules (SGs). While this is normal behavior, persistence of SGs or dysregulation of SG dynamics can promote disease states.
Castaneda and Dao, in collaboration with Taylor's group, showed that UBQLN2 was "recruited" to SGs. "This gives...
Wake Up To Breaking News!