PgmNr Y3053: Mechanism of protein quality control at the inner nuclear membrane in budding yeast.

Authors:
B. Koch; R. Abblett; H. G. Yu


Institutes
Florida State University, Tallahassee, FL.


Keyword: Protein Sorting and Turnover

Abstract:

The nucleus of a eukaryotic cell is enclosed by a double-membrane structure, termed the nuclear envelope, which separates the nucleoplasm from the cytoplasm. The outer and inner membranes of the nuclear envelope have individualized functions within the cell. The outer nuclear membrane is continuous with the endoplasmic reticulum membrane, whereas the inner nuclear membrane acts as the intermediate connecting the outer nuclear membrane to the nucleoplasm. Proteins within the inner nuclear membrane (INM) interact with the telomeres, the nuclear lamina and the nuclear pore complex, and play important roles in chromosome movement and nuclear migration.  Defective INM proteins can lead to genetic diseases, such as Emory driefuss muscular dystrophy.  In order to maintain protein homeostasis at the INM, a specific protein quality control mechanism must be present to remove dysfunctional proteins from the nuclear envelope.  Recent work has shown that some INM proteins are degraded through the Asi-E3 ubiquitin ligase pathway in budding yeast. However other INM proteins, including the SUN-domain protein Mps3, are independent of the Asi pathway for degradation. We report here a novel protein quality control mechanism at the INM that is dependent on protein cleavage.  Using the expression levels of Mps3 as a genetic tool, we found that noncleavable Mps3 forms aggregates at the nuclear periphery and is lethal in vegetative cells.  Genetic analysis demonstrates there is an interaction between the INM proteins and vacuole components, which leads us to propose that certain INM proteins are targeted by the autophagy pathway.  Because the SUN-domain and other INM proteins are conserved from yeast to higher eukaryotes, a similar autophagic regulation of INM proteins may take place in mammalian cells.



Yeast Database Genetic Index
1. gene symbol: mps3; systematic name: YJL019W