The role of neuronal ß2-Adrenergic receptors in the regulation of non-canonical Autophagy in vivo
ANNA KARPOVA (Leibniz Institute for Neurobiology (LIN), Magdeburg)
Amphisomes are autophagy-related organelles formed through the fusion of autophagosomes with late endosomes. In neurons, they are implicated in both cargo degradation and signaling. However, their physiological roles in vivo remain poorly understood.
In this project, we aim to determine how neuronal β₂-adrenergic receptors contribute to amphisome biogenesis and function. To achieve this, we will combine in vitro cell biological and biochemical approaches with viral transgenesis, single-domain antibody-based conformational biosensors, CRISPR-Cas9 genome editing, as well as in vivo optogenetics, chemogenetics, and two-photon imaging to study the impact of the β₂-AR-containing amphisomes on norepinephrine release in locus coeruleus neurons.
References:
Aly A.A.A, …, Karpova A (2025) Activity-dependent control of axonal amphisome trafficking governs norepinephrine release in vivo; doi: https://doi.org/10.1101/2025.09.23.677999
Andres-Alonso M, Schweizer C, .., Karpova A, Reimer R, Virgilio Failla A, Boeckers T.M, Gundelfinger E.D, Kreutz M.R (2025) Amphisome biogenesis couples presynaptic autophagy to local protein synthesis doi: https://doi.org/10.1101/2025.09.23.678051
Oelschlegel AM, …, Karpova A*, Kreutz MR*. (2026) Elevated calneuron-1, an accessory subunit of muscarinic receptors, induces frontotemporal dysconnectivity and schizophrenia-like deficits. Neuron. 114(4):679-698.e11. *co-corresponding authors
Wenger A, …, Karpova A, Kreutz MR, Ahrends R. (2026) High-Fat Diet and a High Amyloid Load Interact to Induce PKC-α Dependent Synaptic Insulin Resistance. Mol Cell Proteomics. 23;25(4):101537.
Freund PA, Panayotis N, …, Karpova A, Burlingame AL, Kreutz MR, Fainzilber M. (2026) Subcellular depletion of importin β1 impairs presynaptic local translation and spatial memory. Sci Signal. 20;19(921):eady2026.
Karpova A, Hiesinger PR, Kuijpers M, Albrecht A, Kirstein J, Andres-Alonso M, Biermeier A, Eickholt BJ, Mikhaylova M, Maglione M, Montenegro-Venegas C, Sigrist SJ, Gundelfinger ED, Haucke V, Kreutz MR. (2025) Neuronal autophagy in the control of synapse function. Neuron. 2025 Apr 2;113(7):974-990.
Karpova A, Aly A.A.A, Levente Marosi E, Mikulovic S (2024) Fiber-based in vivo imaging: unveiling avenues for exploring mechanisms of synaptic plasticity and neuronal adaptations underlying behavior, https://doi.org/10.1117/1.NPh.11.S1.S11507
Mocellin P, … Karpova A, Pakan JMP, Kreutz MR, Mikulovic S, Remy S. (2024) A septal-ventral tegmental area circuit drives exploratory behavior. Neuron.112(6):1020-1032.e7.
Grochowska K.M*, Andres-Alonso M*, Karpova A*, Kreutz M.R (2022) The needs of a synapse – How local organelles serve synaptic proteostasis; EMBO J. 2022 Apr 4;41(7):e110057 *equal contribution
Gundelfinger E.D, Karpova A, Pielot R., Garner C.C, Kreutz M.R. (2022). Organization of Presynaptic Autophagy-Related Processes; Front Synaptic Neurosci. 2022 Mar 17;14:829354, eCollection 2022.
Andres-Alonso M, Kreutz MR*, Karpova A* (2021) Autophagy and the endolysosomal system in presynaptic function. Cell Mol Life Sci, 78(6):2621-2639, *co-corresponding authors
Andres-Alonso M, …, Karpova A*, Kreutz MR* (2019) SIPA1L2 controls trafficking and local signaling of TrkB-containing amphisomes at presynaptic terminals. Nat Commun 10:5448. *co-corresponding authors
Karpova A, Mikhaylova M, … Gundelfinger, E.D., Kreutz, M.R. (2013) Encoding and Transducing the Synaptic or Extrasynaptic Origin of NMDA Receptor Signals to the Nucleus. Cell 152(5):1119-1133
Karpova A, Mikhaylova M, Thomas U, Knöpfel T, Behnisch T. (2006) Involvement of protein synthesis and degradation in long-term potentiation of Schaffer Collateral CA1 synapses, J Neurosci 26(18):4949-4955.
