Fam20C regulates protein secretion by Cab45 phosphorylation

Hecht, Tobias Karl Heinz; Blank, Birgit; Steger, Martin; López, Víctor A.; Beck, Gisela; Ramazanov, Bulat; Mann, Matthias; Tagliabracci, Vincent S.; Blume, Julia von

doi:10.1083/jcb.201910089

Cited by 18 publications

(20 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, recent studies show that Fam20C phosphorylation is required for the secretion of certain proteins. For example, Fam20C phosphorylates calcium binding protein 45 kDa (Cab45), a Golgi protein, regulating the sorting and secretion of proteins ( 84 ). This phosphorylation regulates Cab45 oligomerization independent of its Ca 2+ binding ability and facilitates translocation of Cab45 into trans Golgi network-derived vesicles, thus accelerating vesicle budding ( 84 ).…”

Section: Fam20c the Secreted Golgi Casein Kinasementioning

confidence: 99%

“…For example, Fam20C phosphorylates calcium binding protein 45 kDa (Cab45), a Golgi protein, regulating the sorting and secretion of proteins ( 84 ). This phosphorylation regulates Cab45 oligomerization independent of its Ca 2+ binding ability and facilitates translocation of Cab45 into trans Golgi network-derived vesicles, thus accelerating vesicle budding ( 84 ). Furthermore, the Cab45 phosphorylation enhances secretion of its client proteins, including lysozyme C ( 84 ).…”

Section: Fam20c the Secreted Golgi Casein Kinasementioning

confidence: 99%

“…This phosphorylation regulates Cab45 oligomerization independent of its Ca 2+ binding ability and facilitates translocation of Cab45 into trans Golgi network-derived vesicles, thus accelerating vesicle budding ( 84 ). Furthermore, the Cab45 phosphorylation enhances secretion of its client proteins, including lysozyme C ( 84 ). Similarly, Fam20C phosphorylation has been shown to be important for the secretion of osteopontin ( 64 ).…”

Section: Fam20c the Secreted Golgi Casein Kinasementioning

confidence: 99%

See 2 more Smart Citations

The ABCs of the atypical Fam20 secretory pathway kinases

Worby

Mayfield

Pollak

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

The study of extracellular phosphorylation was initiated in late 19th century when the secreted milk protein, casein, and egg-yolk protein, phosvitin, were shown to be phosphorylated. However, it took more than a century to identify Fam20C, which phosphorylates both casein and phosvitin under physiological conditions. This kinase, along with its family members Fam20A and Fam20B, defined a new family with altered amino acid sequences highly atypical from the canonical 540 kinases comprising the kinome. Fam20B is a glycan kinase that phosphorylates xylose residues and triggers peptidoglycan biosynthesis, a role conserved from sponges to human. The protein kinase, Fam20C, conserved from nematodes to humans, phosphorylates well over 100 substrates in the secretory pathway with overall functions postulated to encompass endoplasmic reticulum homeostasis, nutrition, cardiac function, coagulation, and biomineralization. The preferred phosphorylation motif of Fam20C is SxE/pS, and structural studies revealed that related member Fam20A allosterically activates Fam20C by forming a heterodimeric/tetrameric complex. Fam20A, a pseudokinase, is observed only in vertebrates. Loss-of-function genetic alterations in the Fam20 family lead to human diseases such as amelogenesis imperfecta, nephrocalcinosis, lethal and nonlethal forms of Raine syndrome with major skeletal defects, and altered phosphate homeostasis. Together, these three members of the Fam20 family modulate a diverse network of secretory pathway components playing crucial roles in health and disease. The overarching theme of this review is to highlight the progress that has been made in the emerging field of extracellular phosphorylation and the key roles secretory pathway kinases play in an ever-expanding number of cellular processes.

show abstract

Section: Fam20c the Secreted Golgi Casein Kinasementioning

confidence: 99%

Section: Fam20c the Secreted Golgi Casein Kinasementioning

confidence: 99%

Section: Fam20c the Secreted Golgi Casein Kinasementioning

confidence: 99%

See 1 more Smart Citation

The ABCs of the atypical Fam20 secretory pathway kinases

Worby

Mayfield

Pollak

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…SPCA1 Ca 2+ pumping activity, which is stimulated by recruitment of F-actin via cofilin1 to this protein, is necessary to create regions of high local Ca 2+ concentration in the TGN lumen, which favor the oligomerization of Cab45, a soluble calcium-binding protein localized in the TGN lumen at steady state [ 45 , 47 ]. In addition, phosphorylation of Cab45 by the Golgi-localized soluble protein kinase Fam20C is important for Cab45-mediated cargo sorting and protein secretion [ 144 ]. Notably, Cab45 was shown to be abnormally secreted in cells depleted of either ADF/cofilin or SPCA1, thereby underscoring the importance Cab45 as a Golgi-localized sorting factor [ 44 , 46 ].…”

Section: Lipid Requirements For Pkd-mediated Carts Formationmentioning

confidence: 99%

The PKD-Dependent Biogenesis of TGN-to-Plasma Membrane Transport Carriers

Wakana

Campelo

2021

Cells

View full text Add to dashboard Cite

Membrane trafficking is essential for processing and transport of proteins and lipids and to establish cell compartmentation and tissue organization. Cells respond to their needs and control the quantity and quality of protein secretion accordingly. In this review, we focus on a particular membrane trafficking route from the trans-Golgi network (TGN) to the cell surface: protein kinase D (PKD)-dependent pathway for constitutive secretion mediated by carriers of the TGN to the cell surface (CARTS). Recent findings highlight the importance of lipid signaling by organelle membrane contact sites (MCSs) in this pathway. Finally, we discuss our current understanding of multiple signaling pathways for membrane trafficking regulation mediated by PKD, G protein-coupled receptors (GPCRs), growth factors, metabolites, and mechanosensors.

show abstract

“…The tendency of chromogranin B and secretogranin II to self-aggregate in the mildly acidic, high calcium environment of the TGN is an important factor in granulogenesis [168]; co-aggregation of chromogranin A and secretogranin III also enhances this process [169]. The conformation of Cab45, a calcium binding luminal TGN protein, is regulated by a TGN-localized calcium pump; with calcium bound, Cab45 can oligomerize with secretory proteins such as lysozyme C, affecting their secretion [170,171]. Free calcium, which can reach mM levels in the lumen of the sarcoplasmic reticulum [172], exerts a pH-dependent effect on the self-aggregation of proANP [147,173].…”

Section: Accepted Articlementioning

confidence: 99%

PAM: diverse roles in neuroendocrine cells, cardiomyocytes, and green algae

2021

View full text Add to dashboard Cite

Our understanding of the ways in which peptides are used for communication in the nervous and endocrine systems began with the identification of oxytocin, vasopressin and insulin, each of which is stored in electron dense granules, ready for release in response to an appropriate stimulus. For each of these peptides, entry of its newly synthesized precursor into the endoplasmic reticulum lumen is followed by transport through the secretory pathway, exposing the precursor to a sequence of environments and enzymes that produce the bioactive products stored in mature granules. A final step in the biosynthesis of many peptides is C-terminal amidation by Peptidylglycine -Amidating Monooxygenase (PAM), an ascorbate-and copper-dependent membrane enzyme that enters secretory granules along with its soluble substrates. Biochemical and cell biological studies elucidated the highly conserved mechanism for amidated peptide production and raised many questions about PAM trafficking and the effects of PAM on cytoskeletal organization and gene expression. Phylogenetic studies and the discovery of active PAM in the ciliary membranes of Chlamydomonas reinhardtii, a green alga lacking secretory granules, suggested that a PAM-like enzyme was present in the last eukaryotic common ancestor. While the catalytic features of human and C. reinhardtii PAM are strikingly similar, the trafficking of PAM in C. reinhardtii and neuroendocrine cells and secretion of its amidated products differ. A comparison of PAM function in neuroendocrine cells, atrial myocytes and C. reinhardtii reveals multiple ways in which altered trafficking allows PAM to accomplish different tasks in different species and cell-types.This article is protected by copyright. All rights reserved encoding their precursors revealed the importance of post-translational processing in the production of bioactive peptides [5,6]. With the identification of COOH-terminal amidation as a critical step in the synthesis of peptides like vasopressin, oxytocin, neuropeptide Y, cholecystokinin and -melanocyte stimulating hormone, searches for an amidating enzyme began [7][8][9]. The sequencing of cDNAs encoding the prepropeptides for amidated peptides indicated that each amidated peptide was produced from a precursor with a COOH-terminal glycine.Using bovine and rodent pituitaries, a soluble monooxygenase that converted peptidylglycine substrates into amidated products, peptidylglycine -hydroxylating monooxygenase (PHM; E.C. 1.14.17.3), was identified and shown to require copper and ascorbic acid (Fig. 1A) [9]. The purification of soluble, ~40 kDa PHM led to the expression cloning of a cDNA that encoded a 110 kDa Type I integral membrane protein that included an NH 2terminal signal sequence followed by PHM (Fig. 1A) [10]. With a cDNA in hand, it quickly became apparent that the luminal region of this membrane protein included two catalytic activities, PHM and peptidyl-hydroxyglycine -amidating lyase (PAL; E.C. 4.3.2.5) (Fig. 1A) [7,11]. Under the slightly acidic conditions encountere...

show abstract

Fam20C regulates protein secretion by Cab45 phosphorylation

Cited by 18 publications

References 61 publications

The ABCs of the atypical Fam20 secretory pathway kinases

The ABCs of the atypical Fam20 secretory pathway kinases

The PKD-Dependent Biogenesis of TGN-to-Plasma Membrane Transport Carriers

PAM: diverse roles in neuroendocrine cells, cardiomyocytes, and green algae

Contact Info

Product

Resources

About