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Review
. 2020 Apr 30;69(2):227-244.
doi: 10.33549/physiolres.934229. Epub 2020 Mar 23.

A new look at transudation: the apocrine connection

R Farkaš  1 , M Beňo, D Beňová-Liszeková, I Raška, O Raška
Affiliations
Review

A new look at transudation: the apocrine connection

R Farkaš et al. Physiol Res. .

Abstract

Transcellular trafficking in which various molecules are transported across the interior of a cell, is commonly classified as transcytosis. However, historically this term has been used synonymously with transudation. In both cases transcellular trafficking starts with the internalization of proteins or other compounds on the basal or basolateral side of a cell and continues by their transport across the interior to the apical pole (or vice versa) where they are subsequently released. This allows a cell to release products which are synthesized elsewhere. Here, we discuss the common features of both transcytosis and transudation, and that which differentiates them. It appears that transcytosis and transudation are identical in terms of vesicular import and endosomal sorting of cargo, but completely differ in the re-secretion process. Specialized epithelial cells re-release substantial quantities of the endocytosed material, and often also a great variety. Some recent studies indicate that this is achieved by non-canonical apocrine secretion rather than by the regular vesicular mechanism of exocytosis, and takes place only on the apical pole. This massive re-release of endocytosed proteins, and potentially other compounds via the apocrine mechanism should be considered as transudation, distinct from transcytosis.

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Conflict of interest statement

Conflict of interest

There is no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic illustration of transcytosis. In principle, endocytosis takes place on the basal or basolateral pole of the cell, endocytosed cargo captured in vesicles, which occasionally can fuse, is drawn across the cell, and ejected on the apical side of the cell by exocytosis. There is well-documented evidence that retromer (comprising of Vps26, Vps29, Vps35 and two sorting nexins e.g. SNX1/SNX2, SNX1/SNX5 or SNX5/SNX6) are chiefly involved in the mediation of this clathrin-dependent (gray vesicles) transport via the trans-Golgi network or ER system (yellow vesicles). This route strikingly differs from endosomal trafficking leading to multivesicular bodies (MVB) and lysosomes (brown and dark brown). However, ejection of the vesicles on the apical side can also involve clathrin-independent and caveolin-associated less circuitous route (pink vesicles) that is achieved by direct or close-to-direct movement between basal/basolateral and the apical domains, thus representing a simplified form of transcytosis. Under these circumstances, the cargo is re-exocytosed quickly and without any change. At the same time, the cell can produce its own, distinct secretory vesicles (dark violet) targeted for exocytosis. Large red numbers indicate the three main routes of transcytosis: 1. and 2. utilise clathrin-dependent endocytosis, while 3. is caveole-linked and clathrin-independent. L = lumen.
Fig. 2
Fig. 2
Schematic illustration of transudation. Material endocytosed on the basal or basolateral pole of the cell, in a similar manner as during transcytosis, is released on the apical pole by apocrine secretion, allowing the massive externalization of many more proteins than were endocytosed, and often together with hundreds, if not thousands of the cell own products. In comparison to transcytosis, many more products are re-released than during transcytosis. The initial phases of the process (endocytosis) can utilize the same vesicular mechanisms for internalization on the basal and basolateral pole as during transcytosis, but the subsequent stages are directed towards massive apocrine secretion which is a completely non-vesicular pathway, many of its steps remain enigmatic at the molecular level. Nevertheless, experimental evidence suggests that numerous foreign proteins, produced by distal cells and tissues that are internalized from circulation by endocytosis, are detected among the plethora of products manufactured by the epithelial secretory cell which release them en masse via the apocrine mechanism which involves various cellular components including entire or parts of organelles such as ER, Golgi, mitochondria (orange), microsomes and even unsorted vesicles if they were present at the moment of secretion. L = lumen.
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