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Frontiers in Biology

Front. Biol.    2018, Vol. 13 Issue (6) : 395-405
Intracellular trafficking of planar cell polarity proteins
Yan Huang, Tianji Ma, Yusong Guo()
Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China
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BACKGROUND: Planar cell polarity (PCP) is a phenomenon in which epithelial cells are polarized along the plane of a tissue. PCP is critical for a variety of developmental processes and is regulated by a set of evolutionarily conserved PCP signaling proteins. Many of the PCP proteins adopt characteristic asymmetric localizations on the opposing cellular boundaries. Currently, the molecular mechanisms that establish and maintain this PCP asymmetry remain largely unclear. Newly synthesized integral PCP proteins are transported along the secretory transport pathway to the plasma membranes. Once delivered to the plasma membranes, PCP proteins undergo endocytosis. Recent studies reveal insights into the intracellular trafficking of PCP proteins, suggesting that intracellular trafficking of PCP proteins contributes to establishing the PCP asymmetry.

OBJECTIVE: To understand the intracellular trafficking of planar cell polarity proteins in the secretory transport pathway and endocytic transport pathway.

METHODS: This review summarizes our current understanding of the intracellular trafficking of PCP proteins. We highlights the molecular mechanisms that regulate sorting of PCP proteins into transport vesicles and how the intracellular trafficking process regulates the asymmetric localizations of PCP proteins.

RESULTS: Current studies reveal novel insights into the molecular mechanisms mediating intracellular trafficking of PCP proteins. This process is critical for delivering newly synthesized PCP proteins to their specific destinations, removing the unstable or mislocalized PCP proteins from the plasma membranes and preserving tissue polarity during proliferation of mammalian skin cells.

CONCLUSION: Understanding how PCP proteins are delivered in the secretory and endocytic transport pathway will provide mechanistic insights into how the asymmetric localizations of PCP proteins are established and maintained.

Corresponding Authors: Yusong Guo   
Online First Date: 25 September 2018    Issue Date: 30 November 2018
 Cite this article:   
Yan Huang,Tianji Ma,Yusong Guo. Intracellular trafficking of planar cell polarity proteins[J]. Front. Biol., 2018, 13(6): 395-405.
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Yan Huang
Tianji Ma
Yusong Guo
Fig.1  The asymmetric localizations of PCP proteins in Drosophila pupal wing. PCP proteins show characteristic asymmetric localizations on the opposing cellular boundaries in Drosophila pupal wing. The wing hairs shown in black are all localized at the distal side of the cells and pointing to the distal side of cell boundaries. (inset A and inset B) Magnified views of the asymmetric localizations of PCP proteins on the cell boundary.
Fig.2  Delivery of integral PCP proteins along the secretory transport pathway. Newly synthesized PCP proteins are first translocated into the endoplasmic reticulum (ER). After correct folding and modification, these proteins will be delivered to the Golgi apparatus to receive further modifications. The newly synthesized proteins exit the Golgi at the trans Golgi network (TGN). Subsequently, these transport vesicles are packaged into transport vesicles at the TGN and delivered along sophisticated post-Golgi trafficking routes to the plasma membrane. (inset) A model for sorting of Vangl2 at the ER. The COPII coat subunit, Sar1, binds to GTP and recruits the Sec23/24B complex to the ER membranes forming pre-budding complexes. Subsequently, the Sec23/24B complex recognizes Vangl2 and recruits the Sec13/31 complex. Polymerization of the Sec13/31 complex along with its associated Sec23/24B complex and cargo proteins forms cage structures leading to membrane deformation and release of Vangl2-enriched vesicles from the ER.
Fig.3  Sorting of PCP proteins at the TGN. Vangl2 which represents PCP proteins that are targeted to the proximal side of cell boundaries and Frizzled6 which represents PCP proteins that are targeted to the distal side of cell boundaries are sorted differentially at the TGN by different cargo adaptors. Differential sorting will cause packaging of distal and proximal PCP proteins into distinct transport vesicles. Polarized delivery of these vesicles along the planar polarized microtubule cytoskeleton may contribute to establishing the PCP asymmetry. (inset A) A model demonstrating sorting of Vangl2 at the TGN. GTP-bind Arfrp1 recruits AP-1 to the TGN membrane and promotes a conformational change of AP-1 to allow AP-1 to binds the tyrosine sorting motif on Vangl2 thereby enriching Vangl2 into nascent transport vesicles. (inset B) A model demonstrating sorting of Frizzled6 at the TGN. An unknown Arf family protein, once binding to GTP, recruits the epsinR/clathrin complex to the TGN. At the TGN, the epsinR/clathrin complex binds the polybasic sorting motif on Frizzled6 cytosolic domain to mediate packaging of Frizzled6 into transport vesicles.
Fig.4  The proposed model showing how intracellular trafficking contribute to the asymmetric localizations of PCP proteins. The non-centrosomal microtubules are aligned along the proximal-distal axis with more plus ends on the distal side of cell boundaries. Vesicles enriched with the distally or proximally localized PCP proteins are preferentially delivered to the plus or minus end of the microtubules respectively. The mis-targeted PCP proteins can be removed from the plasma membrane through the endocytic transport process. (inset) Major unanswered questions regarding intracellular trafficking of PCP proteins.
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