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Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
1Correspondence: Department of Cell Biology, Harvard Medical School, 220 Longwood Ave., Boston, MA 02115, USA.
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INTRODUCTION |
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 TOP INTRODUCTION REFERENCES |
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, and, in 1959, Porter and George Pappas
called attention to the close association with the cell surface of
extracellular fibrils that they believed to be composed of collagen in
the process of polymerizing on the fibroblast plasmalemma
(2)
. Observations such as these (2
3
4
5)
led
Porter to propose and defend for some time the theory that collagen
fibrils form by a process of ecdysis or direct shedding of cytoplasmic
filaments through the plasmalemma onto the mesenchymal cell surface.
This hypothesis required newly synthesized collagen to be released from
ribosomes directly into the cytoplasm, rather then to take the route
from the RER through the Golgi apparatus that was being demonstrated at
the same time and the same institute for other secretory proteins by
Porter’s colleagues, Philip Seikevitz and George Palade
(6)
.
Inspired by the latter study (6)
, Jean Paul Revel
and I did an autoradiographic study at the EM level in 1963 using
3H proline as a precursor for collagen, a protein
that consists of 25% proline and hydroxyproline (7)
. Our
data showing tritium localization to the RER, followed by transport to
the Golgi apparatus, were consistent with the idea that chondrocytes
use the same secretory pathways as do pancreatic acinar cells, and,
indeed, it was subsequently shown by EM immunohistochemistry that
procollagen is present only in the RER, Golgi apparatus, and secretory
vacuoles/vesicles of mesenchymal cells (8)
. While
quantitation of autoradiographic studies of intracellular collagen
transport proved difficult (9)
, the conclusion that the
newly synthesized proline-rich products do not significantly accumulate
on the cell surface was unquestionable. Rather, the tritium-labeled
extracellular matrix proteins seem to diffuse through the cartilage
matrix to polymerize some distance from the cells (7)
, and
a similar sequence of events was shown by autoradiography for
deposition of matrix by fibroblasts (9
, 10)
and
odontoblasts (11
, 12)
. Thus, it seems clear that newly
forming collagen is not polymerizing on the plasmalemma of mesenchymal
cells to any significant degree.
What are we to conclude from the convincing demonstration by Porter and
others of the close association of extracellular matrix fibrils with
the fibroblast cell surface? Surely, what was being observed for the
first time at the EM level was the phenomenon that we now call
‘cell-matrix interaction’ (13
, 14)
. In oblique sections
across the plasmalemma, the extracellular fibrils appear to be
continuous with filamentous cortical cytoplasmic material
(2
3
4
5)
, and this observation was extended by Hynes and
Destree (15)
using immunohistochemistry to demonstrate
codistribution with intracellular actin of fibronectin fibrils on the
fibroblast cell surface. The functional consequences of actin-matrix
interaction were subsequently demonstrated in mesenchymal cells by
Tomasek and Hay (16)
and Harkin and Hay (17)
,
and in epithelium by Sugrue and Hay (18)
and others (13,
19). The major family of transmembrane extracellular matrix receptors
that link actin filaments to the matrix are termed integrins, and they
form cytoplasmic complexes with focal adhesion and Src kinases that
transduce signals to the nucleus via MAP kinases and other proteins
(19
, 20)
. Thus, cell and extracellular matrix form a
mutually dependent continuum in the body of the multicellular organism.
The manner in which epithelial cells might control the
polymerization of collagen fibrils at some distance from their cell
surface was a subject that also intrigued Porter. In the 1950s, Paul
Weiss called attention to the elegant orthogonal lattice of collagen
fibrils in the acellular dermis created by the epidermis of aquatic
vertebrates. Later, Porter extended this observation to include the
subepidermal matrix of the lamprey eel and collagenous cuticle of the
annelid worm (5, 13). We showed in 1963 by EM autoradiography that the
newly synthesized collagen of the amphibian subepidermal orthogonal
gridwork is deposited near the basal lamina (basement membrane) and is
subsequently displaced inward by unlabeled matrix after the tritiated
pulse has passed (21)
. Weiss et al. (13)
proposed that a cell-switching mechanism allows each layer to be
deposited in a plywood fashion at right angles to the one previously
formed, but Porter pointed out the many shortcomings of this
hypothesis. With his colleagues, Joe Nadol and John Gibbons, he
proposed in 1969 (22)
the ‘shingle’ or ‘scindulene’
hypothesis, which states that the orthogonal plies are in the form of
narrow groups (shingles), all of which insert into the basal lamina
(Fig. 1A
) and none of which are in the form of discontinuous sheets
as suggested by others. They studied the development of the Fundulus
acellular dermis, which at hatching consists of about 10 orthogonally
arranged layers of collagen fibrils (22)
. Each collagen
ply appears to extend for a limited distance along the epidermal basal
lamina before veering off at a slight angle, owing to its displacement
by the next shingle (Fig. 1B
). The shingles, thus, are not
parallel to the basal lamina but insert into it at an angle of ~3°.
Judged by the tangential sections, growth is accomplished by insertion
of additional fibrils into the basal lamina in each shingle
(22)
. Studying the corneal stroma architecture of birds,
which has the same orthogonal-type lattice as that of the dermis of the
lower vertebrate, we were able to confirm the shingle arrangement of
such orthogonal lattices using more modern preparative techniques (Fig. 1C
) (13)
. It remains to be shown how the
collagen secreted by the epithelium (and underlying fibroblasts, when
present) attaches to the basal lamina and organizes itself into these
orthogonal shingles.
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In summary, I have discussed two major areas of matrix biology to which Keith Porter made seminal contributions. As we noted, progress in understanding cell-matrix interaction has been remarkably rapid. However, we have hardly begun to address the fundamental problem of how the cell controls the dynamic and often very splendid organization of its extracellular matrix.
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ACKNOWLEDGMENTS |
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REFERENCES |
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TOPINTRODUCTIONREFERENCES |
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