Several novel nuclear envelope transmembrane proteins identified in skeletal muscle have cytoskeletal associations.
Nuclear envelopes from liver and a neuroblastoma cell line have previously been analyzed by proteomics; however, most diseases associated with the nuclear envelope affect muscle. To determine whether muscle has unique nuclear envelope proteins, rat skeletal muscle nuclear envelopes were prepared and analyzed by multidimensional protein identification technology. Many novel muscle-specific proteins were identified that did not appear in previous nuclear envelope data sets. Nuclear envelope residence was confirmed for 11 of these by expression of fusion proteins and by antibody staining of muscle tissue cryosections. Moreover, transcript levels for several of the newly identified nuclear envelope transmembrane proteins increased during muscle differentiation using mouse and human in vitro model systems. Some of these proteins tracked with microtubules at the nuclear surface in interphase cells and accumulated at the base of the microtubule spindle in mitotic cells, suggesting they may associate with complexes that connect the nucleus to the cytoskeleton. The finding of tissue-specific proteins in the skeletal muscle nuclear envelope proteome argues the importance of analyzing nuclear envelopes from all tissues linked to disease and suggests that general investigation of tissue differences in organellar proteomes might yield critical insights.
Wilkie
Gavin S
GS
Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
Korfali
Nadia
N
Swanson
Selene K
SK
Malik
Poonam
P
Srsen
Vlastimil
V
Batrakou
Dzmitry G
DG
de las Heras
Jose
J
Zuleger
Nikolaj
N
Kerr
Alastair R W
AR
Florens
Laurence
L
Schirmer
Eric C
EC
D000818:Animals; D002454:Cell Differentiation; D002458:Cell Fractionation; D002460:Cell Line; D003599:Cytoskeleton / Q000378:metabolism*; D006801:Humans; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D009685:Nuclear Envelope / Q000378:metabolism* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
D008565:Membrane Proteins; D009687:Nuclear Proteins