TY - JOUR
T1 - LTK is an ER-resident receptor tyrosine kinase that regulates secretion
AU - Centonze, Federica G.
AU - Reiterer, Veronika
AU - Nalbach, Karsten
AU - Saito, Kota
AU - Pawlowski, Krzysztof
AU - Behrends, Christian
AU - Farhan, Hesso
N1 - Funding Information:
Work in the Farhan laboratory was supported by grants from the Norwegian Research Council (NFR; grant number 262717), the Norwegian Cancer Society (Kreftforeningen; grant number 182815), the Anders Jahre Foundation, the Rakel-Otto-Bruun Legat, the Swiss Science Foundation, and the German Science Foundation (DFG; grant number 271101596). F.G. Centonze is supported by a PhD scholarship from the Institute of Basic Medical Sciences, University of Oslo. K. Pawlowski was supported by a Polish National Science Centre grant (2014/15/B/ NZ1/03359). C. Behrends was supported by the DFG within the framework of the Munich Cluster for Systems Neurology (EXC2145 SyNergy) and the Collaborative Research Center (CRC1177) as well as by the Boehringer Ingelheim Foundation. The authors declare no competing financial interests.
Publisher Copyright:
© 2019 Centonze et al.
PY - 2019
Y1 - 2019
N2 - The endoplasmic reticulum (ER) is a key regulator of cellular proteostasis because it controls folding, sorting, and degradation of secretory proteins. Much has been learned about how environmentally triggered signaling pathways regulate ER function, but only little is known about local signaling at the ER. The identification of ER-resident signaling molecules will help gain a deeper understanding of the regulation of ER function and thus of proteostasis. Here, we show that leukocyte tyrosine kinase (LTK) is an ER-resident receptor tyrosine kinase. Depletion of LTK as well as its pharmacologic inhibition reduces the number of ER exit sites and slows ER-to-Golgi transport. Furthermore, we show that LTK interacts with and phosphorylates Sec12. Expression of a phosphoablating mutant of Sec12 reduces the efficiency of ER export. Thus, LTK-to-Sec12 signaling represents the first example of an ER-resident signaling module with the potential to regulate proteostasis.
AB - The endoplasmic reticulum (ER) is a key regulator of cellular proteostasis because it controls folding, sorting, and degradation of secretory proteins. Much has been learned about how environmentally triggered signaling pathways regulate ER function, but only little is known about local signaling at the ER. The identification of ER-resident signaling molecules will help gain a deeper understanding of the regulation of ER function and thus of proteostasis. Here, we show that leukocyte tyrosine kinase (LTK) is an ER-resident receptor tyrosine kinase. Depletion of LTK as well as its pharmacologic inhibition reduces the number of ER exit sites and slows ER-to-Golgi transport. Furthermore, we show that LTK interacts with and phosphorylates Sec12. Expression of a phosphoablating mutant of Sec12 reduces the efficiency of ER export. Thus, LTK-to-Sec12 signaling represents the first example of an ER-resident signaling module with the potential to regulate proteostasis.
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U2 - 10.1083/jcb.201903068
DO - 10.1083/jcb.201903068
M3 - Article
C2 - 31227593
AN - SCOPUS:85070680480
VL - 218
SP - 2470
EP - 2480
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 8
ER -