Lipid composition dependent binding of apolipoprotein E signal peptide : Importance of membrane cholesterol in protein trafficking

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Soluble secretory and membrane proteins contain a short stretch of signal peptide (SP) at their N-terminal end, which gets cleaved after reaching the destination organelle. However, the importance of SP in protein trafficking is not fully understood. The lipid compositions of cellular organelles are highly heterogeneous, and the preference of SP toward a particular lipid composition might play a key role in unidirectional trafficking of protein. In order to understand the preference of Apolipoprotein E (ApoE) toward endoplasmic reticulum (ER), we have studied the interaction of its SP with membranes of varying lipid compositions. The importance of cholesterol is paramount as subcellular organelles contain differential amount of cholesterol; endoplasmic reticulum (ER) contains the least amount of cholesterol. We have utilized batteries of steady-state and time-resolved fluorescence techniques to understand the affinity of ApoE signal peptide toward membranes of varying lipid compositions. We observed that the ApoE signal peptide binds tightly with membranes devoid of cholesterol, and binding affinity reduces with increasing concentration of membrane cholesterol. Our results clearly suggest the importance of membrane composition in the unidirectional movement of ApoE toward ER. This property of SP can further be utilized for the development of organelle specific cargo delivery.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:291

Enthalten in:

Biophysical chemistry - 291(2022) vom: 15. Dez., Seite 106907

Sprache:

Englisch

Beteiligte Personen:

Mirdha, Lipika [VerfasserIn]
Sengupta, Tanusree [VerfasserIn]
Chakraborty, Hirak [VerfasserIn]

Links:

Volltext

Themen:

97C5T2UQ7J
Apolipoprotein E
Apolipoproteins E
Cholesterol
Journal Article
Protein Sorting Signals
Research Support, Non-U.S. Gov't
Signal peptide

Anmerkungen:

Date Completed 07.11.2022

Date Revised 12.11.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.bpc.2022.106907

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM347435424