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connects the two by forming dimers (
de Brito and Scorrano, 2008
). Other
components, such as the sorting protein PACS2 or the GTPase Rab32, reg-
ulate MAM composition according to cellular requirements (
Myhill et al.,
2008
;
Bui et al., 2010
).
Given that the ER and mitochondria represent the cell's main source
and sink of calcium, respectively (
Berridge, 2002
), it is not surprising that
MAMs play a key role in calcium homeostasis (
Hayashi et al., 2009
). These
interorganelle contacts allow the formation of microdomains of high cal-
cium concentration at the surface of mitochondria, thereby facilitating
rapid ion uptake (
Rizzuto et al., 1998
). Proteins known to be involved in
calcium handling have been shown to be enriched in MAM. Examples
here include IP3Rs (
Mendes et al., 2005
;
Szabadkai et al., 2006
), the RyR
(
García-Pérez et al., 2008
;
Kopach et al., 2008
), the Sig-1R (
Hayashi and
Su, 2007
), and perhaps even calnexin (
Myhill et al., 2008
), emphasizing the
intimate relationship between ER and mitochondria in regulating calcium
homeostasis (
Mironov and Symonchuk, 2006
). Conversely, calcium regu-
lates relative positioning of ER and mitochondria via the autocrine motility
factor receptor (AMFR) (
Wang et al., 2000
), apparently another MAM-
enriched protein (
Registre et al., 2004
;
Goetz and Nabi, 2006
).
ER and mitochondrial dynamics are highly interrelated and their con-
tacts are maintained in spite of this dynamism. Recent data obtained in yeast
demonstrate that the contacts are conserved during mitochondrial fission.
Moreover, fission itself can take place in the ER-mitochondria junctions
(
Friedman et al., 2011
).
Contacts between plasma membrane and ER have been described in
several cell types. The proteins STIM1 at the ER and ORAI1 at the plasma
membrane regulate this interaction when calcium is depleted (
Toulmay
and Prinz, 2011
). Another important group of proteins present in the ER-
plasma membrane contacts is the Osh family. Osh3, for example, localizes
to the contacts according to the level of PI4P. High PI4P levels recruit and
activate Osh3 at contacts sites, leading to its interaction with VAP proteins
in the ER and the activation of phosphatases, such as Sac1 (
Stefan et al.,
2011
).
The ER and Golgi apparatus are functionally linked as constituents of
the secretory pathway; however, direct physical contacts between the two
organelles have been described, as well. Ceramides produced in the ER are
transported to the
trans
-Golgi to be converted to sphingomyelin. In this case,
appropriate trafficking requires the cytosolic protein CERT, which interacts
with VAP on the ER surface (
Kawano et al., 2006
). Another example of
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