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Distinct overlapping sequences at the carboxy-terminus of merlin regulate its tumour suppressor and morphogenic activity.

Laulajainen M, Melikova M, Muranen T, Carpén O, Grönholm M - J. Cell. Mol. Med. (2012)

Bottom Line: In addition to the two full-length merlin isoforms and truncating mutations found in patients, we focused on the evolutionally conserved C-terminal residues 545-547, also harbouring disease-causing mutations.The residues 538-568 were found particularly important for this morphogenic activity.The results further show that both merlin isoforms are able to equally inhibit proliferation, whereas C-terminal mutants affecting residues 545-547 are less effective in growth suppression.

View Article: PubMed Central - PubMed

Affiliation: Biomedicum Helsinki, Department of Pathology, University of Helsinki, Helsinki, Finland. minja.pehrsson@helsinki.fi

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Cytoskeletal components and time-lapse analysis of merlin-induced extensions. (A) Nf2−/− MEFs expressing merlin isoform 2 and 1-547 were stained for merlin and either phalloidin or α-tubulin. Both actin and tubulin are present in longer merlin-induced extensions (arrows). (B) Still pictures from live cell imaging of Nf2−/− MEFs transfected with merlin isoform 2. Arrowheads show the direction of movement and arrows the forming extension. The long extensions are formed when protrusions cannot detach as the cell moves in the opposite direction. (C) Migrating cells used in live cell imaging expressing isoform 2 (left picture) and WT expressing cells (right picture) were stained for merlin. GFP-α-actinin was used to identify isoform 2 expressing cells used in live cell imaging. A gradient of merlin isoform 2 is observed in moving cells in the trailing edge, in addition merlin is present at the leading edge (inset). (D) Nf2−/− MEFs expressing merlin isoform 2 were stained for merlin and endogenous ezrin (left panel). Ezrin does not form a gradient but is present in membrane structures which are devoid of merlin (arrowhead). Mouse embryonic fibroblasts lacking ezrin (ezrin−/− MEFs) expressing merlin isoform 2 were stained for merlin and phalloidin (right picture). A gradient of merlin is detected also in ezrin−/− MEFs.
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fig03: Cytoskeletal components and time-lapse analysis of merlin-induced extensions. (A) Nf2−/− MEFs expressing merlin isoform 2 and 1-547 were stained for merlin and either phalloidin or α-tubulin. Both actin and tubulin are present in longer merlin-induced extensions (arrows). (B) Still pictures from live cell imaging of Nf2−/− MEFs transfected with merlin isoform 2. Arrowheads show the direction of movement and arrows the forming extension. The long extensions are formed when protrusions cannot detach as the cell moves in the opposite direction. (C) Migrating cells used in live cell imaging expressing isoform 2 (left picture) and WT expressing cells (right picture) were stained for merlin. GFP-α-actinin was used to identify isoform 2 expressing cells used in live cell imaging. A gradient of merlin isoform 2 is observed in moving cells in the trailing edge, in addition merlin is present at the leading edge (inset). (D) Nf2−/− MEFs expressing merlin isoform 2 were stained for merlin and endogenous ezrin (left panel). Ezrin does not form a gradient but is present in membrane structures which are devoid of merlin (arrowhead). Mouse embryonic fibroblasts lacking ezrin (ezrin−/− MEFs) expressing merlin isoform 2 were stained for merlin and phalloidin (right picture). A gradient of merlin is detected also in ezrin−/− MEFs.

Mentions: To study the composition of the merlin-induced long protrusions, isoform 2 and 1-547 transfected Nf2−/− MEFs were stained for actin and tubulin. The merlin-induced long processes contained both actin and microtubuli (Fig. 3A), indicating that the extensions are not only actin-containing long filopodia, but represent other membrane structures.


Distinct overlapping sequences at the carboxy-terminus of merlin regulate its tumour suppressor and morphogenic activity.

Laulajainen M, Melikova M, Muranen T, Carpén O, Grönholm M - J. Cell. Mol. Med. (2012)

Cytoskeletal components and time-lapse analysis of merlin-induced extensions. (A) Nf2−/− MEFs expressing merlin isoform 2 and 1-547 were stained for merlin and either phalloidin or α-tubulin. Both actin and tubulin are present in longer merlin-induced extensions (arrows). (B) Still pictures from live cell imaging of Nf2−/− MEFs transfected with merlin isoform 2. Arrowheads show the direction of movement and arrows the forming extension. The long extensions are formed when protrusions cannot detach as the cell moves in the opposite direction. (C) Migrating cells used in live cell imaging expressing isoform 2 (left picture) and WT expressing cells (right picture) were stained for merlin. GFP-α-actinin was used to identify isoform 2 expressing cells used in live cell imaging. A gradient of merlin isoform 2 is observed in moving cells in the trailing edge, in addition merlin is present at the leading edge (inset). (D) Nf2−/− MEFs expressing merlin isoform 2 were stained for merlin and endogenous ezrin (left panel). Ezrin does not form a gradient but is present in membrane structures which are devoid of merlin (arrowhead). Mouse embryonic fibroblasts lacking ezrin (ezrin−/− MEFs) expressing merlin isoform 2 were stained for merlin and phalloidin (right picture). A gradient of merlin is detected also in ezrin−/− MEFs.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3822986&req=5

fig03: Cytoskeletal components and time-lapse analysis of merlin-induced extensions. (A) Nf2−/− MEFs expressing merlin isoform 2 and 1-547 were stained for merlin and either phalloidin or α-tubulin. Both actin and tubulin are present in longer merlin-induced extensions (arrows). (B) Still pictures from live cell imaging of Nf2−/− MEFs transfected with merlin isoform 2. Arrowheads show the direction of movement and arrows the forming extension. The long extensions are formed when protrusions cannot detach as the cell moves in the opposite direction. (C) Migrating cells used in live cell imaging expressing isoform 2 (left picture) and WT expressing cells (right picture) were stained for merlin. GFP-α-actinin was used to identify isoform 2 expressing cells used in live cell imaging. A gradient of merlin isoform 2 is observed in moving cells in the trailing edge, in addition merlin is present at the leading edge (inset). (D) Nf2−/− MEFs expressing merlin isoform 2 were stained for merlin and endogenous ezrin (left panel). Ezrin does not form a gradient but is present in membrane structures which are devoid of merlin (arrowhead). Mouse embryonic fibroblasts lacking ezrin (ezrin−/− MEFs) expressing merlin isoform 2 were stained for merlin and phalloidin (right picture). A gradient of merlin is detected also in ezrin−/− MEFs.
Mentions: To study the composition of the merlin-induced long protrusions, isoform 2 and 1-547 transfected Nf2−/− MEFs were stained for actin and tubulin. The merlin-induced long processes contained both actin and microtubuli (Fig. 3A), indicating that the extensions are not only actin-containing long filopodia, but represent other membrane structures.

Bottom Line: In addition to the two full-length merlin isoforms and truncating mutations found in patients, we focused on the evolutionally conserved C-terminal residues 545-547, also harbouring disease-causing mutations.The residues 538-568 were found particularly important for this morphogenic activity.The results further show that both merlin isoforms are able to equally inhibit proliferation, whereas C-terminal mutants affecting residues 545-547 are less effective in growth suppression.

View Article: PubMed Central - PubMed

Affiliation: Biomedicum Helsinki, Department of Pathology, University of Helsinki, Helsinki, Finland. minja.pehrsson@helsinki.fi

Show MeSH
Related in: MedlinePlus