Vasculature Growth - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 610

10.2.5 Lumenogenesis

The apical membrane initiation site (AMIS) corresponds to one of the earliest
intermediates in lumenogenesis [ 1177 ]. This cell-surface compartment as well as
subjacent vesicles are characterized by the transient accumulation of numerous
apical polarity and transfer proteins. The delivery of apical cargos to specialized
zones of intercellular contacts, AMISs, i.e., the forming lumen, requires exocytosis. 7
The apical membrane initiation site generates the preapical patch , a closed
lumen formed by the newly established apical membranes of adjacent cells that
is bound at its margins by junctional complexes. Opening of the lumen is a
result of ion and water transport. Further organization of membranes, junctional
complexes, cytoskeleton, and organelles creates the mature cyst, i.e., the tight
junction-delineated lumen.
Lumenogenesis thus depends on Rab11a, Rab8a, and Rab8b GTPases and
guanine nucleotide-exchange factor Rab8-interacting protein (RabIn8) [ 1178 ]. 8
Lumen formation, at least in nephron epithelial cells, relies on a Rab11a-RabIn8-
Rab8a axis that recruits Sec15a and cortical polarity GTPase CDC42 9 and promotes
apical exocytosis by enrolling the partitioning-defective protein (Par) complex
with members Par3 and atypical protein kinase-C and multimeric exocyst-tethering
complex subunit Sec10, and exocyst subunit Sec8 to small vesicles and multiple
rudimentary lumens and close to sites of intercellular contacts that constitute early
apical membrane initiation loci.
Rab11a recycling endosomes are involved in the transfer of apical proteins. 10

Exocytosis that depends on Rab11a involves Rab8GEF RabIn8; the latter recruits

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7 The exocyst complex is composed of 8 proteins: Sec3, Sec5, Sec6, Sec8, Sec10, and Sec15, as
well as Exo70 and Exo84.
8 Protein RabIn8 is homologous to Rab3a-interacting protein (RabIn3), hence its name RabIn3-like
protein. Protein RabIn8 stimulates nucleotide exchange on Rab8, but not Rab3a and Rab5, hence
being a Rab8-specific activator [ 1179 ].
9 Monomeric GTPase CDC42 is recruited to PIP 2 -rich sites of forming lumens by annexin-2, where
it recruits atypical protein kinase-C. Annexin-2 resides transiently in Rab11a + vesicles during
lumen formation [ 1178 ].
10 In nephrons, apical proteins, such as podocalyxin and Crumbs polarity complexes are delivered
to Rab11a recycling endosomes. Podocalyxin is a sialoglycoprotein of the CD34 family of

transmembrane sialomucins. It is a constituent of the glycocalyx of podocytes that acts in podocyte
morphogenesis. The apical Crumbs homolog complex keeps the atypical protein kinase-C apical
during complex cellular shape changes. The apical-polarity determinant Crumbs complex is
essential for lumen formation [ 1177 ]. The Crumbs complex associates with the Par complex
directly or via the Crb complex protein Membrane protein, palmitoylated MPP5 of the P55-
like MAGUK (membrane-associated guanylate kinase) subfamily (a.k.a. protein associated with
Lin-7 PALS1). In addition, Crumbs homologs promote the dissociation of Par3 from Par6 and
aPKC, hence allowing Par3 to localize to apicolateral borders during the transition from AMISs to
preapical patches [ 1177 ].

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