FG repeats facilitate integral protein trafficking to the inner nuclear membrane

Abstract

The mechanism for nucleo-cytoplasmic transport of integral membrane proteins is poorly understood compared to transport of soluble molecules. We recently demonstrated that at least four distinct mechanisms can contribute to transport of integral proteins through the peripheral channels of the nuclear pore complex. One of these requires having multiple phenylalanine-glycine (FG) pairings on the integral protein. It also requires the nuclear pore complex protein Nup35, which separately contains FG repeats. FG-repeats on nuclear pore complex proteins in the central channel have been proposed to interact with FGs on transport receptors to facilitate transport of soluble proteins. Here we show that FG repeats occur quite frequently in both transmembrane and soluble proteins identified in multiple separate proteomic analyses of nuclear envelopes. We postulate that the FG repeats enable these proteins to function as their own transport receptors. 

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Figures and Tables

Figure 1 Occurrence of FGs in NE proteins isolated from blood or muscle compared to other proteins encoded in the genome. As the number of FGs per protein increases on the x-axis, an enrichment of FGs in proteins from the NE fractions is observed. (A) When considering transmembrane proteins (determined with TM HMM v2.0 23) with 14 or more FGs the percentage among NETs was more than 40-fold higher than in the set of transmembrane proteins from the rest of the genome. (B) Surprisingly the same analysis done on soluble proteins revealed an even greater enrichment.

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