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The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle.

Lo HP, Nixon SJ, Hall TE, Cowling BS, Ferguson C, Morgan GP, Schieber NL, Fernandez-Rojo MA, Bastiani M, Floetenmeyer M, Martel N, Laporte J, Pilch PF, Parton RG - J. Cell Biol. (2015)

Bottom Line: Caveolae occupied around 50% of the sarcolemmal area predominantly assembled into multilobed rosettes.These rosettes were preferentially disassembled in response to increased membrane tension.Our findings define a conserved and critical role in mechanoprotection for the unique membrane architecture generated by the caveolin-cavin system.

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Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.

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Ultrastructural morphological abnormalities do not affect the relative surface area of cavin-1−/− muscle fibers. (A–D) Single tomogram image from a ruthenium red–labeled WT muscle fiber showing T-tubule connection to the surface via caveolae (A). Tomographic slices (B–D) represent an enlargement of boxed area in A. See Video 2. (E–G) High magnification 3D images of a WT muscle fiber showing T-tubule connection to the surface via caveolae. See Video 3. (H) 3D surface-rendered reconstruction showing T-tubules connecting to the muscle fiber surface via caveolar rosettes. (I–L) Single tomogram image of a ruthenium red–labeled cavin-1−/− muscle fiber showing dilated T-tubules connecting to the surface via vacuoles (I). Tomographic slices (J–L) represent an enlargement of boxed area in I. See Videos 4 and 5. (M) Tomographic slice of a ruthenium red–labeled cavin-1−/− muscle fiber. (N) Surface-rendered reconstruction highlights honeycomb structure of T tubule–connected reticulated networks as previously shown in differentiating muscle cells (Parton et al., 1997) and human CAV3 muscle (Minetti et al., 2002). Reticulated networks are connected to the surface (S) via vacuoles (V). (N1–N3) Tomographic slices of ruthenium red–labeled cavin-1−/− muscle fiber area highlighted in N. See also Fig. S3 (A and B). (O) 3D view of surface-rendered reconstruction of area highlighted in N showing reticulated networks observed in cavin-1−/− muscle (green). Pink highlights connections to the plasma membrane. Bars: (A, I, and M) 500 nm; (B, E, and J) 100 nm; (H, N, N1–N3, and O) 200 nm.
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fig3: Ultrastructural morphological abnormalities do not affect the relative surface area of cavin-1−/− muscle fibers. (A–D) Single tomogram image from a ruthenium red–labeled WT muscle fiber showing T-tubule connection to the surface via caveolae (A). Tomographic slices (B–D) represent an enlargement of boxed area in A. See Video 2. (E–G) High magnification 3D images of a WT muscle fiber showing T-tubule connection to the surface via caveolae. See Video 3. (H) 3D surface-rendered reconstruction showing T-tubules connecting to the muscle fiber surface via caveolar rosettes. (I–L) Single tomogram image of a ruthenium red–labeled cavin-1−/− muscle fiber showing dilated T-tubules connecting to the surface via vacuoles (I). Tomographic slices (J–L) represent an enlargement of boxed area in I. See Videos 4 and 5. (M) Tomographic slice of a ruthenium red–labeled cavin-1−/− muscle fiber. (N) Surface-rendered reconstruction highlights honeycomb structure of T tubule–connected reticulated networks as previously shown in differentiating muscle cells (Parton et al., 1997) and human CAV3 muscle (Minetti et al., 2002). Reticulated networks are connected to the surface (S) via vacuoles (V). (N1–N3) Tomographic slices of ruthenium red–labeled cavin-1−/− muscle fiber area highlighted in N. See also Fig. S3 (A and B). (O) 3D view of surface-rendered reconstruction of area highlighted in N showing reticulated networks observed in cavin-1−/− muscle (green). Pink highlights connections to the plasma membrane. Bars: (A, I, and M) 500 nm; (B, E, and J) 100 nm; (H, N, N1–N3, and O) 200 nm.

Mentions: We further analyzed the organization of the ruthenium red–labeled WT and cavin-1−/− muscle fibers by electron tomography. In WT muscle fibers, T-tubules invariably connected to the muscle fiber surface via surface-connected caveolae (Fig. 3, A–G; and Videos 2 and 3). Surface-rendered reconstruction of the T-tubule system clearly demonstrated the connection of the T-tubule system to the surface via caveolar rosettes (Fig. 3 H). A similar 3D analysis of cavin-1−/− muscle fibers highlighted the abnormal and dilated T-tubule network within the muscle fiber as well as the surface-connected vacuoles (Fig. 3, I–L; and Video 4). In the absence of caveolae, the abnormal T-tubule network connected to the surface of the muscle fiber via the abundant vacuoles (Video 5). The reticular networks observed in thin sections throughout the cavin-1−/− muscle could be shown to be highly complex “honeycomb-like” reticulated networks with multiple connections to the cell surface via large vacuoles (Fig. 3, M–O; and Fig. S3, A and B) and connections to the T-tubule network, including triad junctions (Fig. S1 A).


The caveolin-cavin system plays a conserved and critical role in mechanoprotection of skeletal muscle.

Lo HP, Nixon SJ, Hall TE, Cowling BS, Ferguson C, Morgan GP, Schieber NL, Fernandez-Rojo MA, Bastiani M, Floetenmeyer M, Martel N, Laporte J, Pilch PF, Parton RG - J. Cell Biol. (2015)

Ultrastructural morphological abnormalities do not affect the relative surface area of cavin-1−/− muscle fibers. (A–D) Single tomogram image from a ruthenium red–labeled WT muscle fiber showing T-tubule connection to the surface via caveolae (A). Tomographic slices (B–D) represent an enlargement of boxed area in A. See Video 2. (E–G) High magnification 3D images of a WT muscle fiber showing T-tubule connection to the surface via caveolae. See Video 3. (H) 3D surface-rendered reconstruction showing T-tubules connecting to the muscle fiber surface via caveolar rosettes. (I–L) Single tomogram image of a ruthenium red–labeled cavin-1−/− muscle fiber showing dilated T-tubules connecting to the surface via vacuoles (I). Tomographic slices (J–L) represent an enlargement of boxed area in I. See Videos 4 and 5. (M) Tomographic slice of a ruthenium red–labeled cavin-1−/− muscle fiber. (N) Surface-rendered reconstruction highlights honeycomb structure of T tubule–connected reticulated networks as previously shown in differentiating muscle cells (Parton et al., 1997) and human CAV3 muscle (Minetti et al., 2002). Reticulated networks are connected to the surface (S) via vacuoles (V). (N1–N3) Tomographic slices of ruthenium red–labeled cavin-1−/− muscle fiber area highlighted in N. See also Fig. S3 (A and B). (O) 3D view of surface-rendered reconstruction of area highlighted in N showing reticulated networks observed in cavin-1−/− muscle (green). Pink highlights connections to the plasma membrane. Bars: (A, I, and M) 500 nm; (B, E, and J) 100 nm; (H, N, N1–N3, and O) 200 nm.
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fig3: Ultrastructural morphological abnormalities do not affect the relative surface area of cavin-1−/− muscle fibers. (A–D) Single tomogram image from a ruthenium red–labeled WT muscle fiber showing T-tubule connection to the surface via caveolae (A). Tomographic slices (B–D) represent an enlargement of boxed area in A. See Video 2. (E–G) High magnification 3D images of a WT muscle fiber showing T-tubule connection to the surface via caveolae. See Video 3. (H) 3D surface-rendered reconstruction showing T-tubules connecting to the muscle fiber surface via caveolar rosettes. (I–L) Single tomogram image of a ruthenium red–labeled cavin-1−/− muscle fiber showing dilated T-tubules connecting to the surface via vacuoles (I). Tomographic slices (J–L) represent an enlargement of boxed area in I. See Videos 4 and 5. (M) Tomographic slice of a ruthenium red–labeled cavin-1−/− muscle fiber. (N) Surface-rendered reconstruction highlights honeycomb structure of T tubule–connected reticulated networks as previously shown in differentiating muscle cells (Parton et al., 1997) and human CAV3 muscle (Minetti et al., 2002). Reticulated networks are connected to the surface (S) via vacuoles (V). (N1–N3) Tomographic slices of ruthenium red–labeled cavin-1−/− muscle fiber area highlighted in N. See also Fig. S3 (A and B). (O) 3D view of surface-rendered reconstruction of area highlighted in N showing reticulated networks observed in cavin-1−/− muscle (green). Pink highlights connections to the plasma membrane. Bars: (A, I, and M) 500 nm; (B, E, and J) 100 nm; (H, N, N1–N3, and O) 200 nm.
Mentions: We further analyzed the organization of the ruthenium red–labeled WT and cavin-1−/− muscle fibers by electron tomography. In WT muscle fibers, T-tubules invariably connected to the muscle fiber surface via surface-connected caveolae (Fig. 3, A–G; and Videos 2 and 3). Surface-rendered reconstruction of the T-tubule system clearly demonstrated the connection of the T-tubule system to the surface via caveolar rosettes (Fig. 3 H). A similar 3D analysis of cavin-1−/− muscle fibers highlighted the abnormal and dilated T-tubule network within the muscle fiber as well as the surface-connected vacuoles (Fig. 3, I–L; and Video 4). In the absence of caveolae, the abnormal T-tubule network connected to the surface of the muscle fiber via the abundant vacuoles (Video 5). The reticular networks observed in thin sections throughout the cavin-1−/− muscle could be shown to be highly complex “honeycomb-like” reticulated networks with multiple connections to the cell surface via large vacuoles (Fig. 3, M–O; and Fig. S3, A and B) and connections to the T-tubule network, including triad junctions (Fig. S1 A).

Bottom Line: Caveolae occupied around 50% of the sarcolemmal area predominantly assembled into multilobed rosettes.These rosettes were preferentially disassembled in response to increased membrane tension.Our findings define a conserved and critical role in mechanoprotection for the unique membrane architecture generated by the caveolin-cavin system.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.

Show MeSH
Related in: MedlinePlus