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Sci. STKE, 2 September 2003
[DOI: 10.1126/stke.2003.198.tr4]

Trans-Endocytosis of Notch Receptors into Ligand-Expressing Cells

Helmut Krämer1 and Nancy R. Gough2*

1Center for Basic Neuroscience and Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75235-9111, USA.
2 Science's STKE, American Association for the Advancement of Science, 1200 New York Avenue, N.W., Washington, DC 20005, USA.


*Corresponding author. E-mail: ngough{at}


The animation shows a schematic representation of how trans-endocytosis of Notch into Delta-expressing cells contributes to Notch activation. Notch proteins are receptors that mediate several developmental processes. Notch receptors are activated upon binding transmembrane ligands of the DSL family, such as Delta (δ). Following ligand binding, Notch is cleaved twice. First, Notch is cleaved in its extracellular domain at the S2 site. The subsequent cleavage within Notch's transmembrane domain at the S3 site releases an intracellular domain (N-ICD), which translocates into the nucleus and regulates the transcription of target genes. The cleavage and trans-endocytosis of the Notch extracellular domain (N-ECD) into the ligand-expressing cell facilitates release of the N-ICD.

Press the "Start" button at the bottom right to begin the animation. Click on the subsequent left or right arrows to go backward or forward in the animation.

This animation was created based on Fig. 2 in the Perspective by Krämer (see below) and was prepared by BioCreations ( with the scientific oversight of H. Krämer at Center for Basic Neuroscience and Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX.

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Educational Details

Learning Resource Type: Animation

Context: Undergraduate upper division, graduate, professional (degree program)

Intended Users: Teacher, learner

Intended Educational Use: Teach, learn

Discipline: Cell biology, molecular biology, developmental biology, biochemistry

Keywords: movie, signal transduction, Drosophila, endocytosis, proteolysis, intramembrane proteolysis, cell signaling

Technical Details

Format: Shockwave Flash Object (swf file)

Size: 30.6 kb

Requirements: Macromedia Flash 5 (

Related Resources

Perspective: H. Krämer, RIPping Notch apart: A new role for endocytosis in signal transduction?

Sci. STKE 2000, pe1 (2000). [Summary] [Full Text]

Perspective: Q. Shen, S. Temple, Creating asymmetric cell divisions by skewing endocytosis. Sci. STKE 2002, pe52 (2002). [Summary] [Full Text]

Review: T. E. Golde, C. B. Eckman, Physiologic and pathologic events mediated by intramembranous and juxtamembranous proteolysis. Sci. STKE 2003, re4 (2003). [Gloss] [Abstract] [Full Text]

ST on the Web: Educator Sites (;CAT_9)--BioSciEdNet (BEN) Portal

Limits for Use

Cost: Free

Rights: This material may be downloaded, printed, linked to, and/or redistributed without modification for non-commercial, course teaching purposes only, provided credit to STKE is included by listing the citation for the teaching resource.


Citation: H. Krämer, N. R. Gough, Trans-endocytosis of Notch receptors into ligand-expressing cells. Sci. STKE 2003, tr4 (2003).

© 2003 American Association for the Advancement of Science

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