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Molecular mechanisms of de novo lumen formation

Nature Reviews Molecular Cell Biology volume 15, pages 665–676 (2014)Cite this article

Subjects

Key Points

  • A lumen arising de novo creates a space between or within cells where no space existed before.

  • De novo lumen formation has been studied in several model systems. Despite apparent differences, there are many cell biological commonalities that now justify a unifying overview.

  • A major mechanism of de novo lumen formation is the delivery of membrane material to the apical plasma membrane of the lumen-forming cell, which must be incorporated in a spatially structured manner.

  • Lumen formation can be subdivided into three steps: determining the site of lumen initiation, enlarging the apical domain, and the maturation and stabilization of the lumen.

  • The major cellular machineries needed for tube construction are cell polarity determinants, vesicle-trafficking systems and the cytoskeleton.

  • Although there is currently a good understanding of how material is delivered to the apical membrane during the creation of tubes, an important open question is how the membrane is given its spatial structure.

Abstract

Many organs contain networks of epithelial tubes that transport gases or fluids. A lumen can be generated by tissue that enwraps a pre-existing extracellular space or it can arise de novo either between cells or within a single cell in a position where there was no space previously. Apparently distinct mechanisms of de novo lumen formation observed in vitro — in three-dimensional cultures of endothelial and Madin–Darby canine kidney (MDCK) cells — and in vivo — in zebrafish vasculature, Caenorhabditis elegans excretory cells and the Drosophila melanogaster trachea — in fact share many common features. In all systems, lumen formation involves the structured expansion of the apical plasma membrane through general mechanisms of vesicle transport and of microtubule and actin cytoskeleton regulation.

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Figure 1: Four different mechanisms of de novo lumen formation.
Figure 2: De novo lumen formation in four experimental model systems.
Figure 3: The initiation step in de novo lumen formation.
Figure 4: Mechanisms of apical membrane growth.

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Acknowledgements

The authors thank M. Affolter, S. Caviglia, S. De Renzis, M. Labouesse, S. Luschnig, K. Röper and Y. Schwab for critical comments on the manuscript. Funding was from the DFG (SFB 572 and LE 546/7-1) and EMBO.

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  1. Sara Sigurbjörnsdóttir and Renjith Mathew: These authors contributed equally to this work.

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  1. European Molecular Biology Laboratory, Heidelberg, 69117, Germany

    Sara Sigurbjörnsdóttir, Renjith Mathew & Maria Leptin

  2. Institute of Genetics, University of Cologne, Cologne, D-50674, Germany

    Maria Leptin

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PowerPoint slides

Glossary

Angiogenesis

The process of forming new blood vessels by sprouting from already-established vasculature.

Vasculogenesis

The formation of new blood vessels from a group of endothelial precursors.

Pinocytosis

A mode of endocytosis by which cells non-specifically take up fluid from their surroundings.

Placodes

Polarized embryonic epithelial layers from which an organ or a structure later develops, often through the invagination of the placodes.

Integrin

A transmembrane protein found as a heterodimer of α- and β-subunits that mediates cell adhesion to the extracellular matrix and to neighbouring cells.

Apical membrane initiation site

(AMIS). An early apical domain between cells marking the membrane domain where a lumen will start forming, preceding the formation of a tight-junction-delimited lumen. It is characterized by the accumulation of apical polarity and trafficking proteins.

Podocalyxin

A transmembrane glycoprotein that is a major constituent of the glycocalyx, which is found in the kidney.

Transcytosis

The transport of vesicles between the apical and basolateral membranes of polarized cells. This requires endocytosis from one membrane domain followed by trafficking of those endosomes to the other domain.

Pre-apical patch

(PAP). An apical domain that has developed from the apical membrane initiation site and is found between cells where the lumen has become tight-junction-delimited.

SNARE

A protein superfamily that mediates target specificity and membrane fusion in vesicle trafficking. SNAREs can be divided into v-SNAREs (vesicle) and t-SNAREs (target) on the basis of their localization.

SLP family

(Synaptotagmin-like protein family). A family of proteins that have a conserved synaptotagmin-like homology domain (SHD) at the amino terminus and that are known to control secretion events.

Rhabdomere

A specialized microvillus on the apical surface of a photoreceptor cell that contains the visual pigments.

Spectrin

A large heterotetrameric protein of α- and β-subunits that lines the plasma membrane and plays an important part in plasma membrane integrity and cytoskeletal structure.

Cysteine-rich intestinal protein

(CRIP). A member of the LIM protein family; it is characterized by its two contiguous zinc-finger domains.

Cystic fibrosis transmembrane conductance regulator

An ion channel that transports chloride across epithelial cell membranes.

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Sigurbjörnsdóttir, S., Mathew, R. & Leptin, M. Molecular mechanisms of de novo lumen formation. Nat Rev Mol Cell Biol 15, 665–676 (2014). https://doi.org/10.1038/nrm3871

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