Limits...
Protein oligomerization modulates raft partitioning and apical sorting of GPI-anchored proteins.

Paladino S, Sarnataro D, Pillich R, Tivodar S, Nitsch L, Zurzolo C - J. Cell Biol. (2004)

Bottom Line: Impairment of oligomerization leads to protein missorting.We propose that oligomerization stabilizes GPI-APs into rafts and that this additional step is required for apical sorting of GPI-APs.Two alternative apical sorting models are presented.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Centro di Endocrinologia ed Oncologia Sperimentale, CNR, Università degli Studi di Napoli Federico II, Italy.

ABSTRACT
An essential but insufficient step for apical sorting of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) in epithelial cells is their association with detergent-resistant microdomains (DRMs) or rafts. In this paper, we show that in MDCK cells both apical and basolateral GPI-APs associate with DRMs during their biosynthesis. However, only apical and not basolateral GPI-APs are able to oligomerize into high molecular weight complexes. Protein oligomerization begins in the medial Golgi, concomitantly with DRM association, and is dependent on protein-protein interactions. Impairment of oligomerization leads to protein missorting. We propose that oligomerization stabilizes GPI-APs into rafts and that this additional step is required for apical sorting of GPI-APs. Two alternative apical sorting models are presented.

Show MeSH

Related in: MedlinePlus

Multistep model for apical sorting of GPI-APs in polarized epithelial cells. (1) Raft partitioning. Both apical and basolateral GPI-APs partition with rafts due to chemical affinity of the GPI-APs for rafts. (2) Stabilization/Concentration. Only apical GPI-APs are stabilized into rafts by protein oligomerization, increasing their raft affinity. A putative apical receptor could be involved in this second step. (3) Raft coalescence. Protein oligomerization could lead to coalescence of more rafts with consequent formation of a functional larger raft from which apical vesicles bud. Two alternative mechanisms leading to the formation of apical vesicles are presented: (a) oligomerization/stabilization into rafts is sufficient to drive apical sorting; and (b) oligomerization drives coalescence of more rafts and subsequent formation of an apical vesicle.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2172584&req=5

fig8: Multistep model for apical sorting of GPI-APs in polarized epithelial cells. (1) Raft partitioning. Both apical and basolateral GPI-APs partition with rafts due to chemical affinity of the GPI-APs for rafts. (2) Stabilization/Concentration. Only apical GPI-APs are stabilized into rafts by protein oligomerization, increasing their raft affinity. A putative apical receptor could be involved in this second step. (3) Raft coalescence. Protein oligomerization could lead to coalescence of more rafts with consequent formation of a functional larger raft from which apical vesicles bud. Two alternative mechanisms leading to the formation of apical vesicles are presented: (a) oligomerization/stabilization into rafts is sufficient to drive apical sorting; and (b) oligomerization drives coalescence of more rafts and subsequent formation of an apical vesicle.

Mentions: We propose that oligomerization could promote stabilization of the GPI-APs into rafts leading to their incorporation into apical vesicles. On the contrary GPI-APs monomers having a shorter residency time in rafts would be excluded from apical vesicles. Alternatively protein oligomerization could drive the coalescence of small rafts into a larger raft which would increase the curvature of the membrane (Harder et al., 1998; Roper et al., 2000; Huttner and Zimmerberg, 2001; Ikonen, 2001; Edidin, 2003) and result in the budding of an apical vesicle (Fig. 8, model).


Protein oligomerization modulates raft partitioning and apical sorting of GPI-anchored proteins.

Paladino S, Sarnataro D, Pillich R, Tivodar S, Nitsch L, Zurzolo C - J. Cell Biol. (2004)

Multistep model for apical sorting of GPI-APs in polarized epithelial cells. (1) Raft partitioning. Both apical and basolateral GPI-APs partition with rafts due to chemical affinity of the GPI-APs for rafts. (2) Stabilization/Concentration. Only apical GPI-APs are stabilized into rafts by protein oligomerization, increasing their raft affinity. A putative apical receptor could be involved in this second step. (3) Raft coalescence. Protein oligomerization could lead to coalescence of more rafts with consequent formation of a functional larger raft from which apical vesicles bud. Two alternative mechanisms leading to the formation of apical vesicles are presented: (a) oligomerization/stabilization into rafts is sufficient to drive apical sorting; and (b) oligomerization drives coalescence of more rafts and subsequent formation of an apical vesicle.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172584&req=5

fig8: Multistep model for apical sorting of GPI-APs in polarized epithelial cells. (1) Raft partitioning. Both apical and basolateral GPI-APs partition with rafts due to chemical affinity of the GPI-APs for rafts. (2) Stabilization/Concentration. Only apical GPI-APs are stabilized into rafts by protein oligomerization, increasing their raft affinity. A putative apical receptor could be involved in this second step. (3) Raft coalescence. Protein oligomerization could lead to coalescence of more rafts with consequent formation of a functional larger raft from which apical vesicles bud. Two alternative mechanisms leading to the formation of apical vesicles are presented: (a) oligomerization/stabilization into rafts is sufficient to drive apical sorting; and (b) oligomerization drives coalescence of more rafts and subsequent formation of an apical vesicle.
Mentions: We propose that oligomerization could promote stabilization of the GPI-APs into rafts leading to their incorporation into apical vesicles. On the contrary GPI-APs monomers having a shorter residency time in rafts would be excluded from apical vesicles. Alternatively protein oligomerization could drive the coalescence of small rafts into a larger raft which would increase the curvature of the membrane (Harder et al., 1998; Roper et al., 2000; Huttner and Zimmerberg, 2001; Ikonen, 2001; Edidin, 2003) and result in the budding of an apical vesicle (Fig. 8, model).

Bottom Line: Impairment of oligomerization leads to protein missorting.We propose that oligomerization stabilizes GPI-APs into rafts and that this additional step is required for apical sorting of GPI-APs.Two alternative apical sorting models are presented.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Biologia e Patologia Cellulare e Molecolare, Centro di Endocrinologia ed Oncologia Sperimentale, CNR, Università degli Studi di Napoli Federico II, Italy.

ABSTRACT
An essential but insufficient step for apical sorting of glycosylphosphatidylinositol (GPI)-anchored proteins (GPI-APs) in epithelial cells is their association with detergent-resistant microdomains (DRMs) or rafts. In this paper, we show that in MDCK cells both apical and basolateral GPI-APs associate with DRMs during their biosynthesis. However, only apical and not basolateral GPI-APs are able to oligomerize into high molecular weight complexes. Protein oligomerization begins in the medial Golgi, concomitantly with DRM association, and is dependent on protein-protein interactions. Impairment of oligomerization leads to protein missorting. We propose that oligomerization stabilizes GPI-APs into rafts and that this additional step is required for apical sorting of GPI-APs. Two alternative apical sorting models are presented.

Show MeSH
Related in: MedlinePlus