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Cell Mol Life Sci. 2018 Sep;75(18):3423-3439. doi: 10.1007/s00018-018-2803-2. Epub 2018 Mar 27.

Tetraspanin-enriched microdomains regulate digitation junctions.

Author information

1
Stephenson Cancer Center and Department of Physiology, University of Oklahoma Health Sciences Center, BRC Building West Room 1474, 975 N.E. 10th Street, Oklahoma City, OK, 73104, USA.
2
Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
3
University of Tennessee Health Science Center, Memphis, TN, USA.
4
St. Jude Children's Research Hospital, Memphis, TN, USA.
5
Stephenson Cancer Center and Department of Physiology, University of Oklahoma Health Sciences Center, BRC Building West Room 1474, 975 N.E. 10th Street, Oklahoma City, OK, 73104, USA. xin-zhang-1@ouhsc.edu.

Abstract

Tetraspanins co-emerged with multi-cellular organisms during evolution and are typically localized at the cell–cell interface, [corrected] and form tetraspanin-enriched microdomains (TEMs) by associating with each other and other membrane molecules. Tetraspanins affect various biological functions, but how tetraspanins engage in multi-faceted functions at the cellular level is largely unknown. When cells interact, the membrane microextrusions at the cell-cell interfaces form dynamic, digit-like structures between cells, which we term digitation junctions (DJs). We found that (1) tetraspanins CD9, CD81, and CD82 and (2) TEM-associated molecules integrin α3β1, CD44, EWI2/PGRL, and PI-4P are present in DJs of epithelial, endothelial, and cancer cells. Tetraspanins and their associated molecules also regulate the formation and development of DJs. Moreover, (1) actin cytoskeleton, RhoA, and actomyosin activities and (2) growth factor receptor-Src-MAP kinase signaling, but not PI-3 kinase, regulate DJs. Finally, we showed that DJs consist of various forms in different cells. Thus, DJs are common, interactive structures between cells, and likely affect cell adhesion, migration, and communication. TEMs probably modulate various cell functions through DJs. Our findings highlight that DJ morphogenesis reflects the transition between cell-matrix adhesion and cell-cell adhesion and involves both cell-cell and cell-matrix adhesion molecules.

KEYWORDS:

Cell–cell adhesion; Cell–cell communication; Integrin; Microextrusion; Nanotubule; Tetraspanin

PMID:
29589089
PMCID:
PMC6615572
[Available on 2019-09-01]
DOI:
10.1007/s00018-018-2803-2
[Indexed for MEDLINE]

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