Bettina Winckler


  • BA, Swarthmore College
  • PhD, Massachusetts Institute of Technology
  • Postdoc, Columbia University
  • Postdoc, Yale University

Primary Appointment

  • Professor, Cell Biology


Research Interest(s)

Endosomal function and dysfunction in neurons. Wiring the nervous system in development.

Research Description

Many diseases of the nervous system (neurodevelopmental and neurodegenerative) as well as degenerative and regenerative processes after injury can be traced at the cellular level to disruptions of endolysosomal pathways, including autophagy. For example, Alzheimer’s disease, Huntington’s disease, and nerve injury all show profound defects in endosomal trafficking. This is not surprising given the central role of the endolysosomal system in regulating not only “cellular trash removal,” but also the quantity and quality of signaling cascades. The Winckler lab has unique expertise in studying endolysosomal trafficking in neurons and has shown that endosomes in neurons use different molecular machineries from non-polarized cells (Yap et al., 2008; Yap et al. 2010, Lasiecka et al. 2010; Yap et al. 2012; Lasiecka et al., 2014). We are particularly interested in the roles neuronal-specific proteins, (for example the neuronal-enriched endosomal protein NEEP21) play in neuronal endosomes. We are making extensive use of live imaging to understand the function and regulation of neuronal endosomes. Secondly, we are studying the cellular mechanisms underlying the correct wiring of the nervous system in development, with an emphasis on critical cytoskeletal proteins, such as DCX (doublecortin) and nestin. DCX is genetically linked to a human neurodevelopmental disorder, Lissencephaly. We are using patient alleles of DCX to carry out structure-function analysis of DCX to arrive at a mechanistic understanding of the defects associated with these alleles.

Selected Publications

  • Barford K, Keeler A, McMahon L, McDaniel K, Yap C, Deppmann C, Winckler B. Transcytosis of TrkA leads to diversification of dendritic signaling endosomes. Scientific reports. 2018;8(1): 4715. PMID: 29549340 | PMCID: PMC5856830
  • Winckler B, Faundez V, Maday S, Cai Q, Guimas Almeida C, Zhang H. The Endolysosomal System and Proteostasis: From Development to Degeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2018;38(44): 9364-9374. PMID: 30381428 | PMCID: PMC6209849
  • Yap C, Digilio L, Kruczek K, Roszkowska M, Fu X, Liu J, Winckler B. A dominant dendrite phenotype caused by the disease-associated G253D mutation in doublecortin (DCX) is not due to its endocytosis defect. The Journal of biological chemistry. 2018. PMID: 30291144
  • Yap C, Digilio L, McMahon L, Garcia A, Winckler B. Degradation of dendritic cargos requires Rab7-dependent transport to somatic lysosomes. The Journal of cell biology. 2018. PMID: 29907658
  • Zhang H, Winckler B, Cai Q. Introduction to the special issue on membrane trafficking in neurons. Developmental neurobiology. 2018;78(3): 167-169. PMID: 29453802 | PMCID: PMC5856451
  • Barford K, Keeler A, Deppmann C, Winckler B. TrkA Bumps into Its Future Self. Developmental cell. 2017;42(6): 557-558. PMID: 28950095
  • Barford K, Yap C, Dwyer N, Winckler B. The related neuronal endosomal proteins NEEP21 (Nsg1) and P19 (Nsg2) have divergent expression profiles in vivo. The Journal of comparative neurology. 2017;525(8): 1861-1878. PMID: 28299779 | PMCID: PMC5663458
  • Casanova J, Winckler B. A new Rab7 effector controls phosphoinositide conversion in endosome maturation. The Journal of cell biology. 2017;216(10): 2995-2997. PMID: 28928133 | PMCID: PMC5626559
  • Yap C, Digilio L, McMahon L, Winckler B. The endosomal neuronal proteins Nsg1/NEEP21 and Nsg2/P19 are itinerant, not resident proteins of dendritic endosomes. Scientific reports. 2017;7(1): 10481. PMID: 28874679 | PMCID: PMC5585371
  • Barford K, Deppmann C, Winckler B. The neurotrophin receptor signaling endosome: where trafficking meets signaling. Developmental neurobiology. 2016. PMID: 27503831
  • Lasiecka Z, Winckler B. Studying endosomes in cultured neurons by live-cell imaging. Methods in cell biology. 2016;131 389-408. PMID: 26794525
  • Simons M, Winckler B. Editorial overview: Cellular neuroscience. Current opinion in neurobiology. 2016;39 v-vii. PMID: 27528089
  • Yap C, Digilio L, McMahon L, Roszkowska M, Bott C, Kruczek K, Winckler B. Different Doublecortin (DCX) Patient Alleles Show Distinct Phenotypes in Cultured Neurons: EVIDENCE FOR DIVERGENT LOSS-OF-FUNCTION AND "OFF-PATHWAY" CELLULAR MECHANISMS. The Journal of biological chemistry. 2016;291(52): 26613-26626. PMID: 27799303
  • Digilio L, Yap C, Winckler B. Ctip2-, Satb2-, Prox1-, and GAD65-Expressing Neurons in Rat Cultures: Preponderance of Single- and Double-Positive Cells, and Cell Type-Specific Expression of Neuron-Specific Gene Family Members, Nsg-1 (NEEP21) and Nsg-2 (P19). PloS one. 2015;10(10): e0140010. PMID: 26465886 | PMCID: PMC4605768
  • Yap C, Winckler B. Adapting for endocytosis: roles for endocytic sorting adaptors in directing neural development. Frontiers in cellular neuroscience. 2015;9 119. PMID: 25904845 | PMCID: PMC4389405
  • Lasiecka Z, Yap C, Katz J, Winckler B. Maturational conversion of dendritic early endosomes and their roles in l1-mediated axon growth. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2014;34(44): 14633-43. PMID: 25355216 | PMCID: PMC4212064
  • Dey D, Eckle V, Vitko I, Sullivan K, Lasiecka Z, Winckler B, Stornetta R, Williamson J, Kapur J, Perez-Reyes E. A potassium leak channel silences hyperactive neurons and ameliorates status epilepticus. Epilepsia. 2013;55(2): 203-13. PMID: 24299204 | PMCID: PMC4161023
  • Eckle V, Shcheglovitov A, Vitko I, Dey D, Yap C, Winckler B, Perez-Reyes E. Mechanisms by which a CACNA1H mutation in epilepsy patients increases seizure susceptibility. The Journal of physiology. 2013;592 795-809. PMID: 24277868 | PMCID: PMC3934715
  • Fu X, Brown K, Yap C, Winckler B, Jaiswal J, Liu J. Doublecortin (Dcx) family proteins regulate filamentous actin structure in developing neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2013;33(2): 709-21. PMID: 23303949 | PMCID: PMC3711551
  • Yap C, Winckler B. Acid indigestion in the endosome: linking signaling dysregulation to neurodevelopmental disorders. Neuron. 2013;80(1): 4-6. PMID: 24094097
  • Yap C, Vakulenko M, Kruczek K, Motamedi B, Digilio L, Liu J, Winckler B. Doublecortin (DCX) mediates endocytosis of neurofascin independently of microtubule binding. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2012;32(22): 7439-53. PMID: 22649224 | PMCID: PMC3372911
  • Yap C, Winckler B. Harnessing the power of the endosome to regulate neural development. Neuron. 2012;74(3): 440-51. PMID: 22578496 | PMCID: PMC3351757
  • Lasiecka Z, Winckler B. Mechanisms of polarized membrane trafficking in neurons -- focusing in on endosomes. Molecular and cellular neurosciences. 2011;48(4): 278-87. PMID: 21762782 | PMCID: PMC3205304
  • Winckler B, Choo Yap C. Endocytosis and endosomes at the crossroads of regulating trafficking of axon outgrowth-modifying receptors. Traffic (Copenhagen, Denmark). 2011;12(9): 1099-108. PMID: 21535338 | PMCID: PMC3155643
  • Bettina Winckler: neuronal polarity on her mind. Interviwed by Caitlin Sedwick. The Journal of cell biology. 2010;191(1): 4-5. PMID: 20921132 | PMCID: PMC2953440
  • Dwyer N, Winckler B. TGF-beta receptors PAR-ticipate in axon formation. Cell. 2010;142(1): 21-3. PMID: 20603011
  • Lasiecka Z, Yap C, Caplan S, Winckler B. Neuronal early endosomes require EHD1 for L1/NgCAM trafficking. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2010;30(49): 16485-97. PMID: 21147988 | PMCID: PMC3004753
  • Winckler B, Mellman I. Trafficking guidance receptors. Cold Spring Harbor perspectives in biology. 2010;2(7): a001826. PMID: 20504966 | PMCID: PMC2890194
  • Winckler B, Mellman I. Trafficking guidance receptors. Cold Spring Harbor perspectives in biology. 2010;2(7): a001826. PMID: 20504966 | PMCID: PMC2890194
  • Yap C, Lasiecka Z, Caplan S, Winckler B. Alterations of EHD1/EHD4 protein levels interfere with L1/NgCAM endocytosis in neurons and disrupt axonal targeting. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2010;30(19): 6646-57. PMID: 20463227 | PMCID: PMC2905050
  • Lasiecka Z, Yap C, Vakulenko M, Winckler B. Compartmentalizing the neuronal plasma membrane from axon initial segments to synapses. International review of cell and molecular biology. 2009;272 303-89. PMID: 19121821
  • Yap C, Nokes R, Wisco D, Anderson E, Fölsch H, Winckler B. Pathway selection to the axon depends on multiple targeting signals in NgCAM. Journal of cell science. 2008;121 1514-25. PMID: 18411247
  • Yap C, Wisco D, Kujala P, Lasiecka Z, Cannon J, Chang M, Hirling H, Klumperman J, Winckler B. The somatodendritic endosomal regulator NEEP21 facilitates axonal targeting of L1/NgCAM. The Journal of cell biology. 2008;180(4): 827-42. PMID: 18299352 | PMCID: PMC2265569