Routing of membrane proteins to large dense core vesicles in PC12 cells

Ruth Marx-Rattner, Richard E. Mains

Research output: Contribution to journalArticle

Abstract

Routing of membrane proteins to large dense core vesicles in neuroendocrine cells can depend on information in both the lumenal and cytoplasmic domains. This study in PC12 cells focuses on the routing, cleavage, and secretion of an integral membrane protein, peptidylglycine α-amidating monooxygenase (PAM), examining both endogenous and virally derived membrane PAM. The role of the lumenal catalytic domains in membrane PAM trafficking was examined by replacement with an epitope tag. Virally derived membrane PAM is localized to the perinuclear area and to slender processes where the large dense core vesicles are located. Expression of PAM along with a neuroendocrine-specific endoprotease liberates a soluble monooxygenase domain, yielding regulated secretion of both the monooxygenase and the prohormone convertase from large dense core vesicles. The subcellular distribution of the epitope-substituted version of PAM within the cells is similar to that of membrane PAM, and both proteins are internalized from the plasma membrane. When secretion is stimulated, Serine937 in the cytoplasmic domain of PAM is phosphorylated to a similar extent in endogenous membrane PAM, virally encoded membrane PAM, and epitope-substituted PAM. Thus, the lumenal PAM catalytic domains are not required for routing or phosphorylation of PAM in PC12 cells.

Original languageEnglish (US)
Pages (from-to)113-127
Number of pages15
JournalJournal of Molecular Neuroscience
Volume18
Issue number1-2
StatePublished - 2002
Externally publishedYes

Fingerprint

PC12 Cells
Secretory Vesicles
Mixed Function Oxygenases
Membrane Proteins
Membranes
Epitopes
peptidylglycine monooxygenase
Catalytic Domain
Proprotein Convertases
Neuroendocrine Cells
Phosphorylation
Cell membranes

Keywords

  • Adenovirus
  • Internalization
  • PAM
  • Phosphorylation
  • Prohormone convertase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry
  • Genetics

Cite this

Routing of membrane proteins to large dense core vesicles in PC12 cells. / Marx-Rattner, Ruth; Mains, Richard E.

In: Journal of Molecular Neuroscience, Vol. 18, No. 1-2, 2002, p. 113-127.

Research output: Contribution to journalArticle

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