Molecular mechanisms of de novo lumen formation

Sigurbjörnsdóttir, Sara; Mathew, Renjith; Leptin, Maria

doi:10.1038/nrm3871

Cited by 155 publications

(173 citation statements)

References 91 publications

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“…52,53 The tracheal network transports oxygen to tissues. It originates from segmentally repeated invaginations of the embryonic ectoderm that extend and undergo a series of branching events.…”

Section: Essential Permanent Transport and Dedicated Transient Traffimentioning

confidence: 99%

Rabs on the fly: Functions of Rab GTPases during development

et al. 2017

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The organization of intracellular transport processes is adapted specifically to different cell types, developmental stages, and physiologic requirements. Some protein traffic routes are universal to all cells and constitutively active, while other routes are cell-type specific, transient, and induced under particular conditions only. Small GTPases of the Rab (Ras related in brain) subfamily are conserved across eukaryotes and regulate most intracellular transit pathways. The complete sets of Rab proteins have been identified in model organisms, and molecular principles underlying Rab functions have been uncovered. Rabs provide intracellular landmarks that define intracellular transport sequences. Nevertheless, it remains a challenge to systematically map the subcellular distribution of all Rabs and their functional interrelations. This task requires novel tools to precisely describe and manipulate the Rab machinery in vivo. Here we discuss recent findings about Rab roles during development and we consider novel approaches to investigate Rab functions in vivo.

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Section: Essential Permanent Transport and Dedicated Transient Traffimentioning

confidence: 99%

Rabs on the fly: Functions of Rab GTPases during development

et al. 2017

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“…Apicobasal polarity has been investigated in the context of lumen formation during development or angiogenesis 4,5 but less is known about the molecular basis of apicobasal polarity in quiescent brain endothelial cells, despite the likely importance of this program for the blood-brain barrier. Here we summarize some key findings with the aim to demonstrate that much remains to be learned about apicobasal polarity programs in brain endothelial cells.…”

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confidence: 99%

Apicobasal polarity of brain endothelial cells

Worzfeld

Schwaninger

2015

J Cereb Blood Flow Metab

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Normal brain homeostasis depends on the integrity of the blood-brain barrier that controls the access of nutrients, humoral factors, and immune cells to the CNS. The blood-brain barrier is composed mainly of brain endothelial cells. Forming the interface between two compartments, they are highly polarized. Apical/luminal and basolateral/abluminal membranes differ in their lipid and (glyco-)protein composition, allowing brain endothelial cells to secrete or transport soluble factors in a polarized manner and to maintain blood flow. Here, we summarize the basic concepts of apicobasal cell polarity in brain endothelial cells. To address potential molecular mechanisms underlying apicobasal polarity in brain endothelial cells, we draw on investigations in epithelial cells and discuss how polarity may go awry in neurological diseases.

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“…These results suggest a model for IRG function in forming and maintaining apical tubule structure via regulation of endosomal recycling. KEYWORDS tubulogenesis; trafficking; endosomes; IRG; immunity-related GTPase S MALL tubules are fundamental structures found in a wide range of tissues in multicellular organisms (Lubarsky and Krasnow 2003;Sigurbjornsdottir et al 2014). Luminal diameter regulation occurs after initial tubule formation; mutations exist in a range of species in which tubes form initially, but cannot maintain their luminal diameter, and change shape over times ranging from minutes for some Caenorhabditis elegans mutants to decades for some forms of Schwann cell degradation (Patzko and Shy 2012).…”

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Facilitation of Endosomal Recycling by an IRG Protein Homolog Maintains Apical Tubule Structure in Caenorhabditis elegans

et al. 2016

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Determination of luminal diameter is critical to the function of small single-celled tubes. A series of EXC proteins, including EXC-1, prevent swelling of the tubular excretory canals in Caenorhabditis elegans. In this study, cloning of exc-1 reveals it to encode a homolog of mammalian IRG proteins, which play roles in immune response and autophagy and are associated with Crohn's disease. Mutants in exc-1 accumulate early endosomes, lack recycling endosomes, and exhibit abnormal apical cytoskeletal structure in regions of enlarged tubules. EXC-1 interacts genetically with two other EXC proteins that also affect endosomal trafficking. In yeast two-hybrid assays, wild-type and putative constitutively active EXC-1 binds to the LIM-domain protein EXC-9, whose homolog, cysteine-rich intestinal protein, is enriched in mammalian intestine. These results suggest a model for IRG function in forming and maintaining apical tubule structure via regulation of endosomal recycling. KEYWORDS tubulogenesis; trafficking; endosomes; IRG; immunity-related GTPase S MALL tubules are fundamental structures found in a wide range of tissues in multicellular organisms (Lubarsky and Krasnow 2003;Sigurbjornsdottir et al. 2014). Luminal diameter regulation occurs after initial tubule formation; mutations exist in a range of species in which tubes form initially, but cannot maintain their luminal diameter, and change shape over times ranging from minutes for some Caenorhabditis elegans mutants to decades for some forms of Schwann cell degradation (Patzko and Shy 2012). The mechanisms of maintenance of tube diameter as animals age and grow are still relatively unknown. Mechanosensitive channels on primary cilia projecting into the lumen regulate luminal diameter in multicellular tubes such as blood vessels, nephrons, and biliary ducts (Ware et al. 2011;Martinac 2014), but narrower single-celled tubules such as those of myelinating Schwann cells do not express cilia on their luminal surface (Yoshimura and Takeda 2012).The C. elegans excretory canal cell provides a tractable genetic model for investigating maintenance of luminal diameter in a seamless single-celled tube (Buechner 2002;Sundaram and Buechner 2016). The excretory canal cell is born in midembryogenesis, forms a hollow lumen, and extends both leftward and rightward to the lateral surface, where each side branches and extends canals both anteriorward and posteriorward to form an "H"-shaped structure (Chitwood and Chitwood 1974;Sulston et al. 1983) ( Figure 1A). Once formed, the excretory canals must continue to grow along with the animal. The diameter is tightly controlled, as the lumens taper toward their closed-tip distal ends and expand as the animal ages (Nelson et al. 1983;Sundaram and Buechner 2016). The luminal membrane is surrounded by a thick terminal web similar in appearance to that of intestinal cells and is rich in vacuolar ATPase (Nelson et al. 1983;Oka et al. 1997). Posterior canal extends full-length to the tip of the animal and is of normal diameter, indicat...

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Molecular mechanisms of de novo lumen formation

Cited by 155 publications

References 91 publications

Rabs on the fly: Functions of Rab GTPases during development

Rabs on the fly: Functions of Rab GTPases during development

Apicobasal polarity of brain endothelial cells

Facilitation of Endosomal Recycling by an IRG Protein Homolog Maintains Apical Tubule Structure in Caenorhabditis elegans

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