Oct 15
2021
Research Bit: Nuclear import receptors as modifiers of TDP-43 pathology
The Packard Center welcomed Wilfried Rossoll from the Mayo Clinic to a recent Investigator's meeting.
Date: October 15, 2021
Presenter: Wilfried Rossoll, PhD
Talk Title: Nuclear import receptors as modifiers of TDP-43 pathology
What was the question being asked?
The Rossoll lab is exploring aggregate-associated proteome to understand how to prevent TDP-43 pathology from occurring and spreading across the central nervous system.
Why is this important for ALS research?
Nuclear Import Receptors (NIRs) can restore mislocalized TDP-43 lacking a functional nuclear localization sequence. Using cellular and fly models, the Rossoll lab can show that KPNB1, a protein coding gene, can rescue TDP-43 proteotoxicity.
What was the take-home message?
The process that karyopherin disengagement in FG domains uses to open the nuclear pore for transport is similar to how they disengage aggregates of binding proteins, like TDP-43. Specifically, KPNB1 and other NIRs can reduce detergent-insoluble pathological TDP-43 variants, but does not affect endogenous TDP. This is consistent across cellular models examined.
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