Rhomboid intramembrane protease RHBDL4 triggers ER-export and non-canonical secretion of membrane-anchored TGFα

Rhomboid intramembrane proteases are the enzymes that release active epidermal growth factor receptor (EGFR) ligands in Drosophila and C. elegans, but little is known about their functions in mammals. Here we show that the mammalian rhomboid protease RHBDL4 (also known as Rhbdd1) promotes trafficking of several membrane proteins, including the EGFR ligand TGFα, from the endoplasmic reticulum (ER) to the Golgi apparatus, thereby triggering their secretion by extracellular microvesicles. Our data also demonstrate that RHBDL4-dependent trafficking control is regulated by G-protein coupled receptors, suggesting a role for this rhomboid protease in pathological conditions, including EGFR signaling. We propose that RHBDL4 reorganizes trafficking events within the early secretory pathway in response to GPCR signaling. Our work identifies RHBDL4 as a rheostat that tunes secretion dynamics and abundance of specific membrane protein cargoes.

Sunt in hoc volumine : apologia Edouardi Leei contra quorundam calumnias. Index annotationum prioris libris. Epistola nuncupatoria ad Desideriu[m] Erasmu[m]. Annotationu[m] libri duo, alter in annotatio[n]es prioris aeditionis noui testamenti Desiderij Er

Texto fechado en Lovaina, 1520, tomado de O5v

Crédito rural : informe presentado al Grupo V del 1.er Congreso Ganadero-Agrícola celebrado bajo los auspicios de la Asociación Rural del Uruguay /

"Conclusiones aprobadas por el Congreso en la sesión del 8 de abril de 1895."

Sentencia absolutoria de última instancia dictada en el juicio de responsabilidad seguido al doctor don Francisco Capella y Pons, juez L. de lo civil de 3 er. turno.

Mode of access: Internet.

Geschichte der Israeliten seit der zeit der Maccabäer bis auf unsre tage, nach den quellen bearb.

Mode of access: Internet.

Der yeshive boḥer (oder der yudisher Hamleṭ) : a pyese in 4 aḳten un 6 bilder /

In Yiddish.

Gu yi cong shu : er shi liu zhong / (Qing) Li Shuchang ji.

Mode of access: Internet.

Narodnai͡a Rusʹ. Kruglyĭ god skazanīi, povi͡erīi, obychaev i poslovit͡s russkago naroda.

Mode of access: Internet.

Der feṭer Pini miṭ der mume Reyzi : a naye mayśe, ergets nit gedruḳṭ ... /

Cover title.

Catalogo dos quadros existentes no Real Palacio das Necessidades : pertemcentes à herança de Sua Magestade Er-Rei o Sr. D. Fernando e que hào de ser vendidos em leilào.

Mode of access: Internet.

Quant j'ai ouy le tabourin = Whene'er the tambourine I hear /

At head of title: Trois chansons.

Niwtʻer hay melikʻutʻean masin /

"E.L." was Eruand Lalayean, the moving force within Hayotsʻ Azgayin Ěnkerutʻiwn.

Vergelyking van den republicaenschen met den gregoriaenschen almanach : beginnende van den 1sten Vendemiaire jaer 1 (22 September 1792) dag zyn'er stichtinge, tot den 10 Nivose jaer 14 (laesten December 1805) inclus, tydstip zyn'er vernieting /

Mode of access: Internet.

Zhamanakakitsʻ patmutʻean sewagoyn ējě : 1915i haykakan dēpkʻer : iroghutʻiwnner ew pataskhanatuutʻiwnner /

Includes bibliographical references.