1 Columbia University, Center for Neurobiology and Behavior, New York, NY,
USA
2 Max-Planck-Institut für medizinische Forschung, Heidelberg, Germany
3 Howard Hughes Medical Institute, Center for Cancer Research, MIT, Cambridge,
MA, USA
* Author for correspondence (e-mail: or38{at}columbia.edu)
A recent report by Vogel et al. describes a bioinformatic analysis of
immunoglobulin superfamily (IgSF) members in Caenorhabditis elegans
and Drosophila melanogaster
(Vogel et al., 2003). We have
previously published reports presenting genome-sequence-driven analyses of
worm and fly IgSF members (Hutter et al.,
2000
; Hynes and Zhao,
2000
; Aurelio et al.,
2002
). In Vogel et al. (Vogel
et al., 2003
), these papers are either not cited
(Hynes and Zhao, 2000
;
Aurelio et al., 2002
) or their
content is essentially ignored (Hutter et
al., 2000
), although they cover much of the same ground as the
Vogel et al. paper. Furthermore, the Vogel et al. paper contains errors and
misclassifications of IgSF family members. Given the high degree of interest
in this superfamily, we wish to correct the errors and clarify any
misconceptions caused by the conflation of structural features with functional
characteristics by Vogel et al.
Errors and misinterpretations in the data set
Although in general, initial genome-wide analyses of protein families are rarely free of errors, we think that such errors should not be taken lightly in the context of a refinement of previously published analyses. We list below the errors that we noted.
Classification of IgSF proteins
IgSF proteins are classified in this paper according to their domain
organization. Although this is a useful classification from a structural point
of view, it has only limited implications for the functions of the proteins.
Treating these structural classes as being equivalent to functional classes is
incorrect as members from each class have been shown to have overlapping
functions. For example, most members of the `Cell Surface I protein' class,
classified as `cell adhesion proteins' by Vogel et al., can clearly serve as
signaling molecules (e.g. L1, NCAM, Robo and DSCAM) (reviewed by
Rougon and Hobert, 2003). To
illustrate one example, the Robo IgSF protein is classified as a cell adhesion
protein by Vogel et al., yet it has clearly been demonstrated to be a
signaling molecule acting through the recruitment of intracellular signal
transducing molecules, such as kinases and nucleotide exchange factors
(reviewed by Araujo and Tear,
2003
; Dickson,
2002
; Korey and Van Vactor,
2000
; Patel and Van Vactor,
2002
; Rougon and Hobert,
2003
). Moreover, many proteins in Class I are not sufficiently
well characterized functionally to support their classification as `cell
adhesion proteins'. Also, the vast majority of Class III molecules are not
characterized functionally and may well have structural/adhesive roles, rather
than signaling roles, as the authors imply. Consequently, conclusions made by
the authors about the meaning of the expansion of `functional' classes in
Drosophila (see p. 6326, `Proteins common and specific to Drosophila and C. elegans')
are not justified. The lack of correct assignment of individual IgSF proteins
also calls into question the claim of the authors that the particular nature
of proteins of the Drosophila IgSF repertoire (see p. 6327) "must be one of the
contributing factors responsible for, for example, the formation of a more
complex cellular structure in Drosophila". Perhaps the most
impressive case of expansion of the IgSF repertoire in Drosophila,
the thousands of alternatively spliced isoforms of the IgSF protein DSCAM
(Schmucker et al., 2000
), is
unfortunately not mentioned by Vogel et al.
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