Exo70‐Mediated Recruitment of Nucleoporin Nup62 at the Leading Edge of Migrating Cells is Required for Cell Migration

Abstract

Nucleoporin Nup62 localizes at the central channel of the nuclear pore complex and is essential for nucleocytoplasmic transport. Through its FG-repeat domain, Nup62 regulates nuclear pore permeability and binds nuclear transport receptors. Here, we report that Nup62 interacts directly with Exo70 and colocalizes with Exo70 at the leading edge of migrating cells. Nup62 binds the N-terminal domain of Exo70 through its coiled-coil domain but not through its FG-repeat domain. Selective inhibition of leading edge Nup62 using RNA interference significantly reduces cell migration. Furthermore, Exo70 recruits Nup62 at the plasma membrane and at filopodia. Removal of the Exo70-binding domain of Nup62 prevents leading edge localization of Nup62. Analogous to Exo70, Nup62 cycles between the plasma membrane and the perinuclear recycling compartment. Altogether, we propose that Nup62 not solely regulates access to the cell nucleus, but additionally functions in conjunction with Exo70, a key regulator of exocytosis and actin dynamics, at the leading edge of migrating cells.

Human Immunodeficiency Virus Type 1 (HIV-1) Induces the Cytoplasmic Retention of Heterogeneous Nuclear Ribonucleoprotein A1 by Disrupting Nuclear Import

“…7 In software-generated surface renditions, the dramatic increase in abundance of Nup62 staining at the nuclear envelope and its spreading into the nuclear matrix may represent signals from the recognition of full-length and several proteolytic products of Nup62 by our two antibodies, as suggested (72,78). This observation would be in line with earlier siRNA-mediated Nup62 depletion studies (79) and was partly explained by the authors as a preferential replenishment of Nup62 at the nuclear pore complex, a phenomenon that may be occurring in HIV-1-expressing cells. This would not represent the first relationship between Nup62 and HIV-1, because Nup62 was also found in a complex that is involved in vRNA nucleocytoplasmic transport (80).…”

Selective loss of RPGRIP1-dependent ciliary targeting of NPHP4, RPGR and SDCCAG8 underlies the degeneration of photoreceptor neurons

“…The idv of the immunoblot bands were first corrected by subtracting the idv background of the same area in the corresponding lane. Then, they were normalized to the idv of Nup62 of the same fraction, a nuclear pore protein that copurifies with all subcellular fractions 60 and without any significant changes between wild type and Rpgrip1 nmf247 .Upon normalization, the idv of all four fractions for each of protein in wild type and Rpgrip1 nmf247 were transformed into a percentage scale (total protein=100%). Average values obtained for each fraction of wild type and Rpgrip1 nmf247 were compared using two-sample t -test with assumption of unequal variance at the minimum significance level of 0.05.…”

Nucleoporin Nup62 maintains centrosome homeostasis

“…Similarly, Nup62 was reported to bind heat shock proteins, hsp90, hsp70, p23, and the TPR domain proteins FKBP52 and PP5 during nuclear importation 21 . Nup62 is also reported to bind the N-terminal domain of the exocyst complex component Exo70 through its coiled-coil domain but not through its FG-repeat domain 22 . Clinically, Nup62 was also suggested to play a role in human immunodeficiency virus type 1 (HIV-1) nucleocytoplasmic shuttling 23 and in the degeneration of the basal ganglia.…”