Import to the inner nuclear membrane: a structural perspective

In all eukaryotic cell, form yeast to humans, the Nuclear Pore Complexes provide the main gateway to the nuclear interior. While the transport of soluble cargo’s in and out of the nucleus is relatively well understood, the transport of membrane proteins that reside in the membranes of the nuclear envelope is less well understood. The inner membrane proteins are an important class of proteins as they are involved in organizing the chromatin and positioning and connecting the nucleus within the cell. Their malfunction is associated with a number of genetic diseases jointly called laminopathies. We want to understand how these membrane proteins arrive at the inner membrane after their synthesis at the outside of the nucleus. We used baker’s yeast, a single cell eukaryote, as model organism and two proteins, named Heh1 and Heh2, to unravel the mechanism of transport. Using a combination of microscopy and structural studies, we studied what sorting signals are needed on the membrane proteins, how they interact with the transport chaperones and how their transport depends of the different components of the Nuclear Pore Complex. Thus, our study appends toward the understanding of membrane protein transport.