help on lysossomes

Samuel A. Green sag4y at dayhoff.med.Virginia.EDU
Thu Mar 30 18:32:36 EST 1995


I will start by emphasizing that there probably really is no
good explanation (yet) of why the lysosomal membrane is itself
resistant to hydrolysis by the content proteins.  Of course, I
will continue by offering at least a bit of speculation.  The
two well-characterized resident lysosomal membrane proteins,
lgp-A and lgp-B (LAMP-1 and LAMP-2) are almost exclusively
lumenal in topology, and are very highly glycosylated (16-18
N-linked oligos on 38-42 kDa polypeptides).  They are also
extremely abundant (at least 0.1% of Triton-soluble protein in
NRK cells) and found almost entirely within the lysosomes.  It
is POSSIBLE that what occurs is a sufficiently dense packing of
these proteins such that they form a physical barrier between
the bilayer and the contents.  This fantasy has a morphological
correlate:  the "halo" seen in electron micrographs stained by
conventional means.  This halo corresponds to a thick layer of
reducing sugars (Neiss 1984, Histochemistry 80:603).  I suspect
that these sugars belong to the lgp's.  It has been suggested
that at least the terminal sugars should be hydrolyzed after a
while.  However, Bruce Granger showed that the isoelectric
point of lgp-A does not shift significantly with age.  Either
these proteins recycle to the TGN to re-acquire sialic acid,
for which there is absolutely no precedent, or the sialic acid
on these oligosaccharides is stable in lysosomes.  Why dense
packing would render these proteins resistant to hydrolysis,
and how one could account for turnover of the lysosomal
membrane, are only two of the questions that arise from this
speculation.  Still, it makes at least a little sense out of
the (limited) available data.



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