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Making connections: control of PI kinase signaling at ER‐PM junctions (351.3)
Author(s) -
Manford Andrew,
Emr Scott,
Stefan Christopher
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.351.3
Subject(s) - endoplasmic reticulum , microbiology and biotechnology , organelle , unfolded protein response , crosstalk , cytoplasm , signal transduction , chemistry , cell signaling , biology , physics , optics
Information transfer between intracellular organelles must take place to regulate the size, shape, composition, and function of individual organelles, as well as for normal cell growth and development. The endoplasmic reticulum (ER) forms an expansive membrane network that contacts and participates in crosstalk with several other organelles in the cell, most notably the plasma membrane (PM). ER‐PM junctions have well‐established functions in the movement of signaling molecules, such as lipids and ions, between the ER and PM. However, little is known about the architecture and structural components of ER‐PM junctions. Using a quantitative proteomics approach, we have identified three families of ER‐PM tether proteins in yeast: the VAP proteins Scs2/22, Ist2 (related to the TMEM16 channel family), and the tricalbin proteins Tcb1/2/3 (orthologs of the extended synaptotagmin‐like proteins E‐Syt1/2/3). Loss of the ER tether proteins results in separation of the peripheral ER network from the PM and the accumulation of an ER meshwork in the cytoplasm. The collapse of the cortical ER network leads to ER stress, activation of cellular stress response pathways, and mis‐regulation of phosphoinositide (PI) lipid signaling at the PM. Thus, ER‐PM junctions have critical roles in maintaining the structure and function of the ER, as well as plasma membrane homeostasis. Our results provide a molecular mechanism for ER‐PM contact site formation and fundamental insights into the function of these organelle junctions in the control of PI kinase signaling networks and cellular stress response pathways.