File:SRY nuclear import model.jpg

From Embryology

Original file(800 × 766 pixels, file size: 79 KB, MIME type: image/jpeg)

A model for nuclear import of SRY from normal males and XY females

The distinct nuclear localization signals (NLSs) of SRY use different import pathways.

XY Male XY Females
The cNLS of SRY is recognized by IMPβ, which docks the transport complex at the nuclear pore complex (NPC) followed by translocation through it. After nuclear entry of the complex, RanGTP binds to IMPβ to trigger release of SRY; DNA binding by SRY may also facilitate the release process.

The SRY nNLS can mediate nuclear import through a novel pathway not utilizing conventional nuclear import factors such as IMPs but an unidentified transport factor, TF, possibly calcium-calmodulin.

In the XY females carrying the R75N and R76P mutations, the nNLS-dependent nuclear import pathway is probably nonfunctional, but the cNLS pathway is most likely active because both mutants bind IMPβ normally.

In the XY female carrying the cNLS mutation, R133W, SRY binds IMPβ with reduced affinity due to the direct effect of the mutation; the nNLS pathway is probably functional.

In the XY female carrying the R62G nNLS mutation, reduced IMPβ binding may imply that both pathways are impaired, with the residual R62G protein that is translocated to the nucleus unable to bind DNA efficiently (similar to the R75N mutation), or bend DNA to the correct angle to establish the correct architecture in the chromatin.

Links: Genital - Male Development | Y Chromosome

Reference

Harley VR, Layfield S, Mitchell CL, Forwood JK, John AP, Briggs LJ, McDowall SG & Jans DA. (2003). Defective importin beta recognition and nuclear import of the sex-determining factor SRY are associated with XY sex-reversing mutations. Proc. Natl. Acad. Sci. U.S.A. , 100, 7045-50. PMID: 12764225 DOI.

Original file name: Fig. 4. http://www.pnas.org/content/100/12/7045/F4.large.jpg


Copyright

Proceedings National Academy of Sciences (PNAS) Liberalization of PNAS copyright policy: Noncommercial use freely allowed Note original Author should be contacted for permission to reuse for Educational purposes. See also PNAS Author Rights and Permission FAQs

Cozzarelli NR, Fulton KR, Sullenberger DM. Liberalization of PNAS copyright policy: noncommercial use freely allowed. Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12399. PMID15314225 "Our guiding principle is that, while PNAS retains copyright, anyone can make noncommercial use of work in PNAS without asking our permission, provided that the original source is cited."

Help:Copyright Tutorial

File history

Click on a date/time to view the file as it appeared at that time.

Date/TimeThumbnailDimensionsUserComment
current21:04, 9 November 2010Thumbnail for version as of 21:04, 9 November 2010800 × 766 (79 KB)S8600021 (talk | contribs)==A model for nuclear import of SRY from normal males and XY females== The distinct nuclear localization signals (NLSs) of SRY use different import pathways. The cNLS of SRY is recognized by IMPβ, which docks the transport complex at the nuclear pore

The following 2 pages use this file: