Endoplasmic Reticulum and the Unfolded Protein Response: Dynamics and Metabolic Integration - International Review of Cell and Molecular Biology - page 224

Two different mechanisms of ER tubule elongation along MT exist. The
first, known as tip attachment complex (TAC), involves STIM1, a single-pass
membrane protein mainly localized to the ER. This protein directly inter-
acts with EB1, an MT-plus-end-binding protein ( Grigoriev et al., 2008 ). In
the TAC mechanism, the ER membrane selectively attaches to the grow-
ing end of an MT in regions where ER networks are dense and MT-plus
ends are abundant. This mechanism allows ER tubule stretching dependent
on MT growth. For the second, the Sliding mechanism, the tip of the ER
tubules binds to an existing MT shaft, forming a sliding attachment that
moves toward the plus end of a MT ( Waterman-Storer and Salmon, 1998 ).
This mechanism is faster and more prevalent than TAC, occurring mainly in
MT harboring acetylated α-tubulin ( Friedman et al., 2010 ).
ER tubules are capable of fusion and fission/branching processes, funda-
mental for the formation of the reticulated network ( Anderson and Hetzer,
2007 ). It is known that ER fusion requires GTP and a family of proteins
called atlastins , which possess GTPase activity and belong to the dynamin
superfamily. In vertebrates, three isoforms are known, atlastin 1, 2, 3, and
only one ortholog exists in invertebrates. Atlastins interact with different
ER-shaping proteins, and these interactions are required for the forma-
tion of ER junctions ( Barlowe, 2009 ; Farhan and Hauri, 2009 ; Hu et al.,
2009 ). In Drosophila , depletion of atlastin produces ER fragmentation, while
its overexpression favors ER fusion. In vitro, reconstitution of atlastin in
liposomes promotes GTP-dependent fusion. Moreover, in humans, atlas-
tins take part in the formation of the reticulated network and membrane
remodeling ( Hu et al., 2009 ; Muriel et al., 2009 ).
2.4. Contacts between ER and Other Organelles
Peripheral ER interacts with almost all cytoplasmic organelles. In this con-
text, the ER forms physical contacts with mitochondria, with important
functional implications. In yeast, this physical interaction is mediated by the
ER-mitochondria encounter structure (ERMES), formed by four compo-
nents: the mitochondrial outer-membrane proteins Mdm10 and Mdm34,
the ER integral membrane protein Mmm1, and the cytosolic protein
Mdm12 ( Kornmann et al., 2009 ). In mammals, the contact sites are termed
MAMs, and have a composition that differs from that of the membranes
of other organelles. For one, the MAMs are enriched in cholesterol, which
gives them a characteristic density and architecture ( Hayashi and Fujimoto,
2010 ). Structural proteins that compose the MAM, include Mitofusin-2
(Mfn2), a GTPase protein present on the surface of both organelles that