SUNDAY, DECEMBER 4- Late Abstracts 1 - Molecular Biology of the ...

SUNDAY
Galán C, Dionisio N, Smani T, Salido GM, Rosado JA. The cytoskeleton plays a modulatory role
in the association between STIM1 and the Ca2+ channel subunits Orai1 and TRPC1. Biochem
Pharmacol. 2011;82:400-10.
Nuclear Structure and Function
2013
Proteostatic control of nuclear targeting pathways by the nuclear pore complex protein,
Nup42.
L-K. LIU 1 , C-C. LIN 1 , D. S. Goldfarb 1 ; 1 Biology, University of Rochester, Rochester, NY
Multiple transport receptors ferry nuclear localization signal (NLS)-bearing cargos across the
nuclear pore complex (NPC). The FG-domains of nucleoporins in the NPC are thought to be
required in specific combinations for efficient transport receptor-mediated transports. A model of
multiple independent NPC translocation routes exist for different transport receptors was
presented. Based on this model, direct competition for the same translocation pathway shared
by multiple transport receptors can be expected. In this study, we have found that Nup42
governs a unique stress response that differentially controls import mediated by Kap95/60 and
Kap104. In vivo kinetic analyses show that Kap95/60 and Kap104 compete for limiting docking
sites at Nup42. Binding to Nup42 is the rate-limiting step in import, since the import rates of
Kap95/60 and Kap104 NLS-cargos are faster in nup42 DFG cells. Nup42 collaborates with the
Hsp70s Ssa1/Ssa2 (but not Ssa3/Ssa4) and the co-chaperone Swa2 to differentially control
nuclear targeting by Kap95/60 and Kap104. Specifically, Kap95/60 import is favored over
Kap104 import when Ssa1/Ssa2 levels are high, such as in response to heat shock or nutrient
depletion. In contrast, Kap104 import is favored when the free Hsp70 pool is depleted, for
example, by sequestration into Huntingtin polyQ protein aggregates. Kap123-mediated import
rates are unaffected by this regulatory circuit. Here we present the first evidence that two
specific transport receptors, Kap95/60 and Kap104, share and compete for similar translocation
route in the NPC. We also conclude that Nup42 is a Kap-specific gatekeeper that controls
import rates in response to proteostatic stress.
2014
Evidence of asymmetric assembly pathway of Nuclear Pore Complex.
P. Colombi 1 , C. Vogel 1 , P. Lusk 1 ; 1 Department of Cell Biology, Yale School of Medicine, New
Haven, CT
In an effort to investigate regulatory mechanisms governing nuclear pore complex (NPC)
assembly, we investigated alterations in the subcellular distribution of multiple nucleoporins
(Nups) through the cell cycle in the budding yeast S. cerevisiae. Consistent with the idea that
NPC assembly is under the control of cell cycle regulators, we observe that several specific
Nups accumulate in the cytoplasm of cells arrested in S-phase but not in G1. Interestingly,
these likely NPC intermediates accumulate asymmetrically between the mother and bud and
appear to be strikingly biased towards the bud, often accumulating at the bud cortex. These
intermediates can often be observed integrating into the daughter cell nuclear envelope during
anaphase supporting the idea that there is a pathway in which Nups are specifically targeted to
the bud to be incorporated in the NPC of the daughter cell. Perturbing this pathway by
conditionally sequestering specific newly synthesized Nups results in a decrease in the size of
daughter nuclei. Most strikingly, these daughter cells are no longer able to progress through the
cell cycle, whereas the mother cells continue to divide. Together these results support the