Dunking into the Lipid Bilayer: How Direct Membrane Binding of Nucleoporins Can Contribute to Nuclear Pore Complex Structure and Assembly

Abstract

Nuclear pore complexes (NPCs) mediate the selective and highly efficient transport between the cytoplasm and the nucleus. They are embedded in the two membrane structure of the nuclear envelope at sites where these two membranes are fused to pores. A few transmembrane proteins are an integral part of NPCs and thought to anchor these complexes in the nuclear envelope. In addition, a number of nucleoporins without membrane spanning domains interact with the pore membrane. Here we review our current knowledge of how these proteins interact with the membrane and how this interaction can contribute to NPC assembly, stability and function as well as shaping of the pore membrane.

Ndc1 drives nuclear pore complex assembly independent of membrane biogenesis to promote nuclear formation and growth

“…There are three transmembrane-containing nucleoporins in metazoans: gp210 ( Gerace et al, 1982 ), Ndc1 ( Mansfeld et al, 2006 ; Stavru et al, 2006 ), and Pom121 ( Hallberg et al, 1993 ) as well as several peripheral membrane binding Nups ( Hamed and Antonin, 2021 ). gp210 is not ubiquitously expressed and is important for mammalian muscle differentiation ( D’Angelo et al, 2012 ; Raices et al, 2017 ) and breakdown of the NE ( Galy et al, 2008 ).…”

“…Nup53 recruits Nup155, which assembles proximal to the pore membrane ( Dultz et al, 2008 ; De Magistris et al, 2018 ; Eisenhardt et al, 2014 ; Franz et al, 2005 ; Hampoelz et al, 2019a ; Lin and Hoelz, 2019 ; Vollmer et al, 2012 ). Nup155 and Nup53 interact with Pom121 and Ndc1 and also contain amphipathic helices that insert into membranes ( Hamed and Antonin, 2021 ; Mitchell et al, 2010 ; von Appen et al, 2015 ). The interaction between Ndc1 and Nup53 is conserved in budding yeast ( Onischenko et al, 2009 ); however, only the interphase pathway of NPC assembly exists in fungi because they undergo a closed mitosis ( Kutay et al, 2021 ).…”

“…The interaction between Ndc1 and Nup53 is conserved in budding yeast ( Onischenko et al, 2009 ); however, only the interphase pathway of NPC assembly exists in fungi because they undergo a closed mitosis ( Kutay et al, 2021 ). Some evidence suggests a functional interaction between Ndc1 and Pom121 and members of the Nup107/160 complex ( Mitchell et al, 2010 ), which also include Nups that directly bind to bilayer lipids ( Drin et al, 2007 ; Hamed and Antonin, 2021 ). Thus, there are multiple connections that link the NPC to the pore membrane, yet their precise roles in NPC assembly remain poorly understood.…”

An amphipathic helix in Brl1 is required for membrane fusion during nuclear pore complex biogenesis in S. cerevisiae

“…Amphipathic helices are short motifs capable of binding lipid bilayers and they have been implicated in bending membranes by inserting into one leaflet of a bilayer, generating a convex curvature (Ford et al 2002; Wang et al 2016). Interestingly, AHs are structural features of many membrane-binding NUPs (Hamed and Antonin 2021) and likely target NUPs to the NPC by curvature sensing (Floch et al 2015). The amphipathic helix in Brl1 (ahBrl1) is highly conserved between organisms with closed mitosis (Figure 5C), suggesting that it could play a critical role in NPC biogenesis, for example by mediating the INM-ONM fusion.…”

“…Amphipathic helices are short motifs capable of binding lipid bilayers and they have been implicated in bending membranes by inserting into one leaflet of a bilayer, generating a convex curvature (Ford et al 2002;Wang et al 2016). Interestingly, AHs are structural features of many membrane-binding NUPs (Hamed and Antonin 2021) and likely target NUPs to the NPC by curvature sensing (Floch et al 2015).…”