William H. Schubert

Intracellular Retention of Glycosylphosphatidyl Inositol-Linked Proteins in Caveolin-Deficient Cells

ABSTRACT The relationship between glycosylphosphatidyl inositol (GPI)-linked proteins and caveolins remains controversial. Here, we derived fibroblasts from Cav-1 null mouse embryos to study the behavior of GPI-linked proteins in the absence of caveolins. These cells lack morphological caveolae, do not express caveolin-1, and show a ∼95% down-regulation in caveolin-2 expression; these cells also do not express caveolin-3, a muscle-specific caveolin family member. As such, these caveolin-deficient cells represent an ideal tool to study the role of caveolins in GPI-linked protein sorting. We show that in Cav-1 null cells GPI-linked proteins are preferentially retained in an intracellular compartment that we identify as the Golgi complex. This intracellular pool of GPI-linked proteins is not degraded and remains associated with intracellular lipid rafts as judged by its Triton insolubility. In contrast, GPI-linked proteins are transported to the plasma membrane in wild-type cells, as expected. Furthermore, recombinant expression of caveolin-1 or caveolin-3, but not caveolin-2, in Cav-1 null cells complements this phenotype and restores the cell surface expression of GPI-linked proteins. This is perhaps surprising, as GPI-linked proteins are confined to the exoplasmic leaflet of the membrane, while caveolins are cytoplasmically oriented membrane proteins. As caveolin-1 normally undergoes palmitoylation on three cysteine residues (133, 143, and 156), we speculated that palmitoylation might mechanistically couple caveolin-1 to GPI-linked proteins. In support of this hypothesis, we show that palmitoylation of caveolin-1 on residues 143 and 156, but not residue 133, is required to restore cell surface expression of GPI-linked proteins in this complementation assay. We also show that another lipid raft-associated protein, c-Src, is retained intracellularly in Cav-1 null cells. Thus, Golgi-associated caveolins and caveola-like vesicles could represent part of the transport machinery that is necessary for efficiently moving lipid rafts and their associated proteins from the trans-Golgi to the plasma membrane. In further support of these findings, GPI-linked proteins were also retained intracellularly in tissue samples derived from Cav-1 null mice (i.e., lung endothelial and renal epithelial cells) and Cav-3 null mice (skeletal muscle fibers).

Recalibrating Educational Research: Toward a Focus on Practice:

and a 4-page, double-spaced paper are required. Both should be typewritten. Examples of abstracts may be found in journals published by the American Psychological Association. Abstracts and papers should be titled and should not contain the name(s) of the author(s) and affiliation(s). Proposals must be submitted with an official Application Form. C o l l o q u i u m Proposal R e q u i r e m e n t s . A 150-word abstract and an 8-page, double-spaced preview describing alland an 8-page, double-spaced preview describing all contributions and their interrelationships are required. All material should be typewritten. Examples of abstracts may be found in journals published by the American Psychological Association. Abstracts and previews should be titled and should not contain the names of the contributors and their affiliations. Proposals must be submitted with an official Application Form. N u m b e r of Cop ies . Five copies of the abstract and the paper or the colloquium preview are necessary. Photocopies or mimeographed copies are acceptable. C r i t e r i a for Proposals . Reports of research will be judged in terms of the significance of the topic, the quality of the theoretical/conceptual rationale, the adequacy of the methods for collecting evidence, the analysis of the evidence and the interpretations and/or conclusions. Reviews of research will be judged in terms of the significance of the topic, balance in coverage of literature, and quality of the critical analysis. Incomplete proposals will be returned. W h e r e to O b t a i n App l ica t ion F o r m . Research Department, International Reading Association, 800 Barksdale Road, PO Box 8139, Newark, Delaware 19711,

Genetic ablation of caveolin-1 in mammary epithelial cells increases milk production and hyper-activates STAT5a signaling

Caveolin-1 (Cav-1) is the main structural protein of caveolae, plasma membrane invaginations that have been implicated in a number of cellular processes, including vesicular transport, cholesterol homeostasis, and the regulation of signal transduction. Previous in vivo studies have established a correlation between Cav-1 expression levels and milk production. In the normal mouse mammary gland, Cav-1 levels were shown to be down-regulated during late pregnancy and lactation, via a Ras-p42/44 MAPK mechanism. Conversely, mammary glands from Cav-1 null (-/-) mice exhibit premature lactation, with augmented development of the lobulo-alveolar compartment and hyper-activation of Jak-2/ STAT5a signaling cascade. However, it remains unknown whether these phenotypes are cell-autonomous, i.e. intrinsic to the alveolar epithelial cells, or whether stromal or adipocyte-secreted factors contribute. To directly address this issue, we have isolated primary mammary epithelial cells from wild-type (WT) or Cav-1 null (-/-) mammary glands. We cultured them either in a 2D model (monolayers of mammary epithelial cells) or in a 3D system on exogenous basement membrane (Matrigel; to reconstitute the minimal lactating unit, i.e. mammary acinus). We show here that Cav-1 deficient mammary epithelial cells display the ability to spontaneously generate milk droplets, and to secrete them into the acinar lumen. Interestingly, such milk production occurs in the absence of lactogenic stimulation. Our results show that monolayers of Cav-1 null mammary epithelial cells are enriched in milk droplets, as judged by both i) phase contrast and ii) immunofluorescence analysis with an antiserum directed against mouse milk proteins. Consistently, Cav-1 deficient acini display increased milk production and secretion, as evaluated by Western blot analysis and electron microscopic examination. Mechanistically, we show that loss of Cav-1 in mammary epithelial cells induces the baseline constitutive hyper-activation of STAT5a signaling, which normally controls the temporal progression of lactogenesis in the mammary gland.

The Return of Curriculum Inquiry from Schooling to Education

Curriculum inquiry is, indeed, a domain that can be characterized by expansion. Since its birth near the turn of this century, its tendency has been to proliferate and fork in many directions, almost simultaneously. Review of curriculum literature throughout the 20th century (Schubert, 1980a) reveals that expansion is not unique to the past few years. At least three dominant tendencies emerged to offer perspectives on the problem of perpetuating universal schooling. Intellectual traditionalists, who advocated study of the classics, hoped that schooling would provide awareness of perennial human problems and perhaps even insights into the paradigmatic structure of the disciplines of knowledge. In practice, such ideals were often dashed in mundane advocacy of subject curricula. Social behaviorists, enamored with the technology of science and the efficiency of business and industry, hoped that schools would mass produce students who could perform activities that contributed to what they determined was successful living. In practice, this did much to atomize and fragment the educative process, reducing it to sets of activities to be delivered by schools. At the same time, experientialists emerged who saw schools as places to perpetuate individual and democratic growth, by having students resolve problems that inhibited meaning and direction in their lives. Although the intent, as expressed by Herbart, Dewey, and others, was to move students from psychological to logical knowledge, practice often debilitated into the provision of adult-dominated projects, disconnected reenactments of human history, or rule by childhood caprice. These tendencies are not only found at the onset of this century; they have correlates that appear again and again under different labels and in different forms. In addition to this emergence of varied perspectives on curriculum thought, curriculum inquiry expanded in another way: new topics were given specialized treatment. Some, e.g., Bobbitt (1924) and Harap (1928), moved from advancing perspectives to providing guidelines or recipes that could be followed by administrators and supervisors of curriculum in schools. Even more specialized treatments focused on curriculum at each of the several levels of schooling: secondary, elementary, junior high,

What is Worthwhile: From Knowing and Needing to Being and Sharing

Jason Michael Lukasik is a Ph.D. candidate in curriculum studies at the University of Illinois at Chicago. His dissertation analyzes the hidden colonial curriculum of zoos through the medium of a fictional novel. He teaches courses in educational foundations and curriculum studies at Northeastern Illinois University and Concordia University Chicago where he is an adjunct instructor. He can be reached at jason.lukasik@mac.com.

Reconceptualizing and the Matter of Paradigms

Schubert observes that emergent recon ceptualization in teacher education has roots in curriculum studies and in dis course about paradigms of inquiry that has at least a 25 year history in natural sciences, humanities, social sciences, and professional studies. He explores hermeneutic and critical strands of re conceptualization from curriculum liter ature and delineates questions raised for the critique of the empirical-analytic paradigm.

Teaching John Dewey as a Utopian Pragmatist While Learning from My Students

Education and the American Creed More than any other figure of the past century, Dewey promoted and strengthened the belief in education as the principal conclusion of the American creed. Among the multitude of cultures that find conflict in American and global society, Dewey envisioned an overarching intercultural education to build a sense of unity through diversity. He conceived of community not as a group set against other groups by special interests, but as a cosmopolitan association of people who draw their strength through finding common cause through their diverse talents. He never doubted the democratic prospect and was an activist for virtually every democratic social movement—educational opportunity, human rights, child welfare, academic freedom, and social justice. He advised his fellow philosophers that they should study the problems of humanity rather than the problems of philosophy. Throughout his life and over the course of a half-century since his passing, John Dewey has been vilified, honored, betrayed, vindicated, attacked and defended. But when all is said and done, he gave America and the world the most provocative, comprehensive, and powerful vision for human progress through democracy and education for the twenty-first century. He was a man for his times and a man for all times. He knew full well that progress is never made. By its very nature, progress is in the making.

The SAGE guide to curriculum in education

The SAGE Guide to Curriculum in Education integrates, summarizes, and explains, in highly accessible form, foundational knowledge and information about the field of curriculum with brief, simply written overviews for people outside of or new to the field of education. This Guide supports study, research, and instruction, with content that permits quick access to basic information, accompanied by references to more in-depth presentations in other published sources. This Guide lies between the sophistication of a handbook and the brevity of an encyclopedia. It addresses the ties between and controversies over public debate, policy making, university scholarship, and school practice. While tracing complex traditions, trajectories, and evolutions of curriculum scholarship, the Guide illuminates how curriculum ideas, issues, perspectives, and possibilities can be translated into public debate, school practice, policy making, and life of the general public focusing on the aims of education for a better human condition. 55 topical chapters are organized into four parts: Subject Matter as Curriculum, Teachers as Curriculum, Students as Curriculum, and Milieu as Curriculum based upon the conceptualization of curriculum commonplaces by Joseph J. Schwab: subject matter, teachers, learners, and milieu. The Guide highlights and explicates how the four commonplaces are interdependent and interconnected in the decision-making processes that involve local and state school boards and government agencies, educational institutions, and curriculum stakeholders at all levels that address the central curriculum questions: What is worthwhile? What is worth knowing, needing, experiencing, doing, being, becoming, overcoming, sharing, contributing, wondering, and imagining? The Guide benefits undergraduate and graduate students, curriculum professors, teachers, teacher educators, parents, educational leaders, policy makers, media writers, public intellectuals, and other educational workers. Key Features: Each chapter inspires readers to understand why the particular topic is a cutting edge curriculum topic; what are the pressing issues and contemporary concerns about the topic; what historical, social, political, economic, geographical, cultural, linguistic, ecological, etc. contexts surrounding the topic area; how the topic, relevant practical and policy ramifications, and contextual embodiment can be understood by theoretical perspectives; and how forms of inquiry and modes of representation or expression in the topic area are crucial to develop understanding for and make impact on practice, policy, context, and theory. Further readings and resources are provided for readers to explore topics in more details.

John Dewey Lives

This dialogue is an edited version of a dialogue between William C. Ayers and William H. Schubert at the November10–12, 2011, meeting of the Progressive Education Network hosted by the Francis W. Parker School in Chicago, Illinois. It was the opening keynote session on the evening of November 10. Ayers interviewed Schubert, who acted as John Dewey. The keynote addressed the contemporary relevance of Dewey for today’s educational issues in general and in particular for the audience of leaders and teachers in progressive schools. Special focus was placed on both extant criticisms of progressive ideas and practices and the relevance and power of Dewey’s ideas for improving education, social action, equity, and democracy today.

Play: A Basis for Becoming an Educational Researcher

As I pondered how, why, where, and when I have become an educational researcher, my somersaulting mind stopped time-after-time on play – and then rolled on. Play for children is their most serious work. Early childhood educators from Friedrich Froebel and Maria Montessori to Erik Erikson and Fred (Mister) Rogers have shown this with great verve.