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The nuclear pore complex protein NDC 1 is involved in
nuclear positioning in migrating fibroblasts
Daniel S. Osorio, Joana Borrego-Pinto
and Edgar R. Gomes
Université Pierre et Marie Curie (Paris 6), Paris, France
Positioning of the nucleus within cells has a role in different
processes such as cell migration and muscle differentiation. In
migrating fibroblasts the nucleus moves backwards prior to cell
migration and this active movement is dependent on the actin
cytoskeleton and on nuclear envelope proteins members of the
LINC complex Nesprin-2 and SUN2. In order to identify novel
proteins involved in this process we preformed a live-imaging
screen for inhibition of nuclear movement through RNA interference (RNAi) against a set of 230 potential/confirmed nuclear
envelope proteins from published organellar proteomics studies.
NDC1, a conserved transmembrane protein of the nuclear pore
complex (NPC) was one of our hits. The screening results were
further confirmed by the inhibition of centrosome reorientation
and nuclear positioning in a fixed cell assay. Although a full
knock down of Ndc1 caused general disruptions of the nuclear
envelope, consistent with its role in nuclear pore assembly, a
partial knockdown was sufficient to inhibit nuclear movement
without significantly affecting nuclear envelope proteins and
structure. Furthermore we identified a specific interaction between
the N-terminal region of Ndc1 and SUN2, distinct from the
proposed NPC interacting region on the conserved C-terminus.
Given that SUN2 and NPC do not seem to co-localize in the NE,
we propose that a subpopulation of non-NPC Ndc1 is involved in
stabilizing SUN2 during nuclear movement