Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration - International Review of Cell and Molecular Biology - page 218

membrane invaginations, while the invagination and tubulation processes
are possible due to the participation of caveolin 3, amphiphysin 2 and dys-
ferlin among others. In addition, a number of proteins play important roles
in stabilizing the triad structure in skeletal muscle, including mitsugumins,
junctophilins, myotubularin, ryanodine receptor (RyR), and the dihydro-
pyridine receptor (Cav1.1 calcium channel) ( Al-Qusairi and Laporte, 2011 ).
2.1.2. Nuclear Envelope
The NE is a highly specialized and selectively permeable double membrane
that surrounds the genetic material of the cell. Electron microscopic anal-
ysis revealed early on that NE and ER form a continuous structure ( Watson,
1955 ), sharing some common components, while others, like nuclear pore-
forming nucleoporins (NUPs), are specific for the NE. Other important
components are the transmembrane proteins of the NE, which interact
with laminin, a protein localized in the internal surface of the NE, and with
chromatin, thereby participating in anchorage of the genetic material and in
gene regulation. On the other hand, KASH domain-containing proteins are
small transmembrane proteins at the external face of the NE that associate
with cytoskeletal proteins, thus determining the shape and positioning of
the NE ( Hetzer, 2010 ).
The NE is a highly dynamic structure, which is modulated during dif-
ferent stages of the cell cycle. In stage G2, the nucleus must duplicate its
size by not only increasing its volume, but also by duplicating its NE proteins;
during mitosis, specifically in prophase, the NE disintegrates. The processes
that lead to dismantling of the NE are not fully understood, however, these
events are preceded by loss of NUPs and transfer of the NE proteins to the
mitotic ER. Following anaphase, NE restructuring occurs and terminates in
complete morphological and functional restructuring of the nucleus. Our
understanding of the NE restoration process is controversial, as there are two
leading theories. The first suggests that the NE is fragmented into small
vesicles that are not degraded completely during mitosis and subsequently
merge to restructure the NE. The second theory proposes that the ER dif-
ferentiates into the NE, which is supported by the mitotic ER structure and
enriched in NE proteins ( Hetzer, 2010 ).
2.1.3. Lipid-Raft-like Domains
Lipid rafts are cholesterol-rich plasma membrane domains which may con-
tain caveolin. Lipid-raft-like domains are defined as caveolin-free plasma
membrane regions enriched in cholesterol and members of the prohibitin