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Lee Goodglick

Publications and source records attributed to Lee Goodglick.

23 records · Page 2Linked to original sources
PubMed2003

Epithelial membrane protein-2 is expressed in discrete anatomical regions of the eye.

Epithelial membrane protein-2 (EMP2) is a member of the four transmembrane superfamily (TM4SF) and is thought to mediate trafficking of diverse proteins such as alpha6beta1 integrin and MHC class I to lipid raft microdomains. EMP2 has also recently been recognized as a putative tumor suppressor gene in certain model systems. Normally, EMP2 is expressed at discrete locations in the body including high levels in the eye, lung, heart, thyroid, and uterus. Here we examine in detail the subanatomic distribution of EMP2 in murine and human ocular tissue. We observe that EMP2 is localized to epithelial layers of the cornea, ciliary body, and retinal pigmented epithelium-choroid, the stromal layers of the sclera, and the nerve fiber layer of the retina and optic nerve. This distribution is distinct from other TM4SF proteins and may relate to a role in apical membrane recycling.

Animals↗
PubMed2003

The tetraspan protein EMP2 increases surface expression of class I major histocompatibility complex proteins and susceptibility to CTL-mediated cell death.

Dysregulation of class I major histocompatibility (MHC1) expression is an important mechanism of immunologic resistance for certain virus-infected or neoplastic cells. This study characterizes a new molecule affecting MHC1 expression and CTL cytotoxicity. Epithelial membrane protein 2 (EMP2) is a tetraspan protein recently identified for its role in suppressing B lymphoma tumorigenicity. The biochemistry of EMP2 suggests that it regulates the surface expression of certain membrane proteins, notably those destined for lipid raft microdomains. In this study, retroviral overexpression of EMP2 in target cells increased their susceptibility to CTL cytotoxicity. Conversely, down-expression of EMP2 using an EMP2-specific ribozyme rendered target cells CTL-resistant. EMP2 expression increased the surface levels of MHC1, CD54, and GM1 glycolipids. Biochemical fractionation indicated that these molecules reside with EMP2 in a lipid raft membrane compartment. Among MHC1 proteins, surface display of H-2D was particularly dependent on EMP2 expression, and blocking antibodies demonstrated that H-2D was critical for allogeneic CTL recognition. This study demonstrates an unexpected role for a tetraspan protein in CTL-mediated cell death and MHC1 surface trafficking.

3T3 Cells↗
PubMed2003

BetaB1-crystallin: identification of a candidate ciliary body uveitis antigen.

PURPOSE: Perineuclear anti-neutrophil cytoplasmic antibody (pANCA), a marker antibody present in 12% of patients with anterior uveitis, recognizes cytoplasmic antigens in the nonpigmented ciliary body epithelium, a probable site of immunologic reactivity in this inflammatory disease. In this study, a recombinantly isolated pANCA monoclonal antibody was used to identify the corresponding antigenic target(s) in the ciliary body. METHODS: Proteins from microdissected eye bank ocular ciliary body tissue were used to identify the corresponding ANCA antigen. Parallel two-dimensional protein gels were used for simultaneous identification of candidate antigenic protein spots by Western blot analysis and as a source of material for proteomic analysis. Multiple independent methods including Western blot analysis, confocal microscopy, and RT-PCR were used to provide additional characterization of the candidate protein. RESULTS: Proteomic analysis suggested that beta B1 (betaB1)-crystallin is the primary ciliary body antigen. The presence of betaB1-crystallin in the human ciliary body was confirmed by Western blot with a betaB1 specific anti-peptide antibody. Confocal microscopy revealed colocalization of the antigenic reactivity of both anti-betaB1 antibody and monoclonal pANCA. RT-PCR confirmed the presence of betaB1-crystallin RNA in the ciliary body tissues. CONCLUSIONS: This study identified betaB1-crystallin as a new cytoplasmic ciliary body antigenic target of a marker autoantibody associated with uveitis. This characterization of betaB1-crystallin outside the lens raises questions about its extralenticular expression, intracellular role, and potential target of inflammation in uveitis.

Amino Acid Sequence↗
PubMed2002

The tetraspan protein epithelial membrane protein-2 interacts with beta1 integrins and regulates adhesion.

The growth arrest-specific-3 (GAS3)/PMP22 proteins are members of the four-transmembrane (tetraspan) superfamily. Although the function of these proteins is poorly understood, GAS3/PMP22 proteins have been implicated in the control of growth and progression of certain cancers. Epithelial membrane protein-2 (EMP2), a GAS3/PMP22 family member, was recently identified as a putative tumor suppressor gene. Here, we addressed the normal function of EMP2 by testing the prediction that it influences integrin-related cell functions. We observed that EMP2 associates with the beta(1) integrin subunit. Co-immunoprecipitation and immunodepletion experiments indicated that approximately 60% of beta(1) integrins and EMP2 can be isolated in common protein complexes. Whereas this association between EMP2 and beta(1) integrin may be direct or indirect, it has features of integrin heterodimer selectivity. Thus, by laser confocal microscopy, EMP2 colocalized with alpha(6)beta(1) but not alpha(5)beta(1) integrin. Increased expression of EMP2 also influenced the integrin heterodimer repertoire present on the plasma membrane. EMP2 specifically increased the surface expression of the alpha(6)beta(1) integrin while decreasing that of the alpha(5)beta(1) protein. Reciprocally, reduction in EMP2 expression using a specific ribozyme decreased surface expression of alpha(6)beta(1) integrin. Accordingly, these EMP2-mediated changes resulted in a dramatic alteration in cellular adhesion to extracellular matrix proteins. This study demonstrates for the first time the interaction of a GAS3/PMP22 family member with an integrin protein and suggests that such interactions and their functional consequences are a physiologic role of GAS3/PMP22 proteins.

3T3 Cells↗