Multiple mechanisms actively target the SUN protein UNC-84 to the inner nuclear membrane

Tapley, Erin C.; Ly, Nina; Starr, Daniel A.

doi:10.1091/mbc.e10-08-0733

Cited by 40 publications

(61 citation statements)

References 57 publications

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“…We previously used this technique to locate the transmembrane domain in UNC-84, as well as multiple sorting motifs in the N-terminus required for INM localization. 27 …”

Section: Sun Proteins and Nuclear Envelope Spacingmentioning

confidence: 99%

SUN proteins and nuclear envelope spacing

Cain

Starr

2014

Nucleus

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T he nuclear envelope consists of 2 membranes separated by 30-50 nm, but how the 2 membranes are evenly spaced has been an open question in the field. Nuclear envelope bridges composed of inner nuclear membrane SUN proteins and outer nuclear membrane KASH proteins have been proposed to set and regulate nuclear envelope spacing. We tested this hypothesis directly by examining nuclear envelope spacing in Caenorhabditis elegans animals lacking UNC-84, the sole somatic SUN protein. SUN/ KASH bridges are not required to maintain even nuclear envelope spacing in most tissues. However, UNC-84 is required for even spacing in body wall muscle nuclei. Shortening UNC-84 by 300 amino acids did not narrow the nuclear envelope space. While SUN proteins may play a role in maintaining nuclear envelope spacing in cells experiencing forces, our data suggest they are dispensable in most cells.

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“…We previously used this technique to locate the transmembrane domain in UNC-84, as well as multiple sorting motifs in the N-terminus required for INM localization. 27 …”

Section: Sun Proteins and Nuclear Envelope Spacingmentioning

confidence: 99%

SUN proteins and nuclear envelope spacing

Cain

Starr

2014

Nucleus

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“…The screen presented here was designed to identify novel mechanisms that function in parallel to SUN-KASH bridges. Our model system, C. elegans larval P-cell nuclear migration, is better suited for identifying such pathways than embryonic dorsal hyp7 precursors where the mechanisms of UNC-84 and UNC-83 were elucidated (McGee et al 2006;Meyerzon et al 2009;Tapley et al 2011). SUN-KASH bridges are absolutely required for nuclear migration in the embryonic hypodermis at all temperatures.…”

Section: Discussionmentioning

confidence: 99%

“…RT-PCR was performed as previously described . For Western analysis, total worm lysate was made, separated by SDS-PAGE, and transferred to a membrane as described (Tapley et al 2011). Anti-TOCA-1 rabbit serum (1:1000) (Giuliani et al 2009) and monoclonal anti-a-tubulin mouse antibody (1:1000) (Clone DM 1A; Sigma, St. Louis) were used as primary antibodies.…”

Section: Rt-pcr and Western Analysismentioning

confidence: 99%

“…Mutations in either of the Caenorhabditis elegans unc-83 and unc-84 genes disrupt nuclear migration in a number of cells, including embryonic hyp7 precursors, intestinal primordial cells, the distal tip cell of the somatic gonad, the one-cell embryo, and larval hypodermal P cells (Sulston and Horvitz 1981;Malone et al 1999;Starr et al 2001;Xiong et al 2011). In our nuclearenvelope bridging model, the SUN protein UNC-84 is targeted to the inner nuclear membrane with its conserved SUN domain in the perinuclear space and its N terminus in the nucleoplasm, where it can interact with lamin (Malone et al 1999;Lee et al 2002;McGee et al 2006;Tapley et al 2011). UNC-84 then recruits the KASH protein UNC-83 to the outer nuclear membrane through a direct interaction between SUN and KASH domains in the perinuclear space (Starr et al 2001;McGee et al 2006;Mellad et al 2011).…”

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confidence: 99%

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toca-1 Is in a Novel Pathway That Functions in Parallel with a SUN-KASH Nuclear Envelope Bridge to Move Nuclei in Caenorhabditis elegans

et al. 2013

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Moving the nucleus to an intracellular location is critical to many fundamental cell and developmental processes, including cell migration, differentiation, fertilization, and establishment of cellular polarity. Bridges of SUN and KASH proteins span the nuclear envelope and mediate many nuclear positioning events, but other pathways function independently through poorly characterized mechanisms. To identify and characterize novel mechanisms of nuclear migration, we conducted a nonbiased forward genetic screen for mutations that enhanced the nuclear migration defect of unc-84, which encodes a SUN protein. In Caenorhabditis elegans larvae, failure of hypodermal P-cell nuclear migration results in uncoordinated and egg-laying-defective animals. The process of P-cell nuclear migration in unc-84 null animals is temperature sensitive; at 25°migration fails in unc-84 mutants, but at 15°the migration occurs normally. We hypothesized that an additional pathway functions in parallel to the unc-84 pathway to move P-cell nuclei at 15°. In support of our hypothesis, forward genetic screens isolated eight emu (enhancer of the nuclear migration defect of unc-84) mutations that disrupt nuclear migration only in a null unc-84 background. The yc20 mutant was determined to carry a mutation in the toca-1 gene. TOCA-1 functions to move P-cell nuclei in a cell-autonomous manner. TOCA-1 is conserved in humans, where it functions to nucleate and organize actin during endocytosis. Therefore, we have uncovered a player in a previously unknown, likely actindependent, pathway that functions to move nuclei in parallel to SUN-KASH bridges. The other emu mutations potentially represent other components of this novel pathway.

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“…3B) (Daryabeigi et al, 2016;Tapley et al, 2011;Hasan et al, 2006;Graumann et al, 2010;Chen et al, 2014). Human SUN2, UNC-84 and plant SUN1 and SUN2 all contain an NLS (Turgay et al, 2010;Graumann et al, 2010;Tapley et al, 2011). The NLS of human SUN2 has been shown to directly bind to the importin-α-importin-β heterodimer, which might mediate its transport through the NPC (Fig.…”

Section: Trafficking Of Sun Proteins Across the Npc For Inm Localizationmentioning

confidence: 99%

The LINC and NPC relationship – it's complicated!

Jahed

Soheilypour

Peyro

et al. 2016

Journal of Cell Science

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The genetic information of eukaryotic cells is enclosed within a double-layered nuclear envelope, which comprises an inner and outer nuclear membrane. Several transmembrane proteins locate to the nuclear envelope; however, only two integral protein complexes span the nuclear envelope and connect the inside of the nucleus to the cytoplasm. The nuclear pore complex (NPC) acts as a gateway for molecular exchange between the interior of the nucleus and the cytoplasm, whereas so-called LINC complexes physically link the nucleoskeleton and the cytoskeleton. In this Commentary, we will discuss recent studies that have established direct functional associations between these two complexes. The assembly of NPCs and their even distribution throughout the nuclear envelope is dependent on components of the LINC complex. Additionally, LINC complex formation is dependent on the successful localization of inner nuclear membrane components of LINC complexes and their transport through the NPC. Furthermore, the architecture of the nuclear envelope depends on both protein complexes. Finally, we will present recent evidence showing that LINC complexes can affect nucleo-cytoplasmic transport through the NPC, further highlighting the importance of understanding the associations of these essential complexes at the nuclear envelope.

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Multiple mechanisms actively target the SUN protein UNC-84 to the inner nuclear membrane

Cited by 40 publications

References 57 publications

SUN proteins and nuclear envelope spacing

SUN proteins and nuclear envelope spacing

toca-1 Is in a Novel Pathway That Functions in Parallel with a SUN-KASH Nuclear Envelope Bridge to Move Nuclei in Caenorhabditis elegans

The LINC and NPC relationship – it's complicated!

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